Podcasts about mnng

This week, we take a look back at the year that was and forward toward what's to come in this new year for the Minnesota National Guard and Minneapolis VA Health Care System. Guests include: MG Shawn Manke – Minnesota National Guard Director Patrick Kelly – Minneapolis VA Health Care System The post MNNG and VA Year in Review appeared first on Minnesota Military Radio.

This week we meet with the Commander of the 148th Fighter Wing, learn about the Minnesota National Guard Youth Camp and get an update from the Minnesota Association of County Veterans Service Officers. Guests include: Col. Nathan Aysta – 148th … Continue reading → The post 148th Fighter Wing and MNNG Youth Camp appeared first on Minnesota Military Radio.

This week we learn about the Minnesota National Guard’s Diversity & Inclusion Special Emphasis Program. Discuss how the Minnesota Department of Veterans Affairs SOAR Program is helping Veterans in need and get an update from the Minnesota Association of County … Continue reading → The post MNNG’s Special Emphasis Program and MDVA’s SOAR Program appeared first on Minnesota Military Radio.

This week we meet with the Senior Enlisted Leaders of the Minnesota National Guard, meet with a representative for the Minneapolis-Richfield American Legion Post 435 to learn about the proposed Veterans Village and get an update from the MN Patriot … Continue reading → The post MNNG Senior Leadership and Veterans Village appeared first on Minnesota Military Radio.

This week we discuss fitness and nutrition in the Minnesota National Guard, learn about working for the Minnesota Department of Veterans Affairs and get an update from the Minnesota Association of County Veterans Service Officers. Guests include: Maj. Jolene Carlson … Continue reading → The post Nutrition at the MNNG and Working at the MDVA appeared first on Minnesota Military Radio.

This week we host our annual Year in Review show with the Adjutant General of the Minnesota National Guard and the Director of the Minneapolis VA Health Care System. Guests include: Maj. Gen. Shawn Manke – Minnesota National Guard Dir. … Continue reading → The post MNNG and VA Year in Review appeared first on Minnesota Military Radio.

This week we discuss the PACT Act with the Veterans Benefits Administration (VBA), U.S. Department of Veterans Affairs, learn about Holiday Support from Minnesota Family Programs and get an update from the Minnesota Association of County Veterans Service Officers. Guests … Continue reading → The post Veterans Benefits Administration and MNNG Family Programs appeared first on Minnesota Military Radio.

This week we meet the newest member of the Minnesota National Guard Chaplaincy, learn about job opportunities and what it’s like to work for the Minnesota Department of Veterans Affairs and get an update from the Minnesota Association of County … Continue reading → The post MNNG’s Newest Chaplain and Working for MDVA appeared first on Minnesota Military Radio.

This week we host our annual Minnesota National Guard and Minnesota Department of Veterans Affairs Year in Review Show and get an update from the Minnesota Association of County Veterans Service Officers. Guests include: Commissioner Larry Herke – Minnesota Department … Continue reading → The post MNNG and MDVA Year in Review appeared first on Minnesota Military Radio.

A berry vine found in Asia proves useful in combating lung cancer Okayama University (Japan), August 17, 2021 Lung cancer is known to be the most fatal form of cancer. Chemicals like 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) found in tobacco are usually the main culprits behind smoking-related lung cancer causing cancer biologists to actively explore targeted treatments. Now, a research group led by Associate Professor ARIMOTO-KOBAYASHI Sakae at Okayama University has reported the potential of a berry-producing vine, Vitis coignetiae Pulliat (colloquially known as Yamabudo in Japan), against lung cancer in mice. The team has previously shown that juice extracted from the Yamabudo fruit and 2,6-dimethoxy-1,4-benzoquinone (DBQ), a chemical found within it, have protective effects against skin cancer. Thus, in this study the potential of both these chemicals was investigated. Mice were first treated with NNK to establish lung cancer models and tumors that subsequently developed within their lungs were assessed. After 30 weeks, mice given Yamabudo juice or DBQ showed greatly reduced tumor size. To understand the mechanism of Yamabudo further, human lung cancer cells were employed. NNK induces cancer by facilitating a chemical change in the DNA structure, known as DNA methylation. To mimic this process, cells were exposed to MNNG (a chemical that artificially induces DNA methylation) and the effects of Yamabudo were studied. Indeed, cells that were treated with Yamabudo juice or DBQ showed lower levels of DNA methylation.  The DNA methylation induced by NNK also plays a role in mutating the DNA, making all exposed cells susceptible to cancer. The methylated forms of DNA tend to form large complexes which can undergo damage more easily. Therefore, NNK-induced mutations were analyzed next to see if Yamabudo also plays a protective role in this regard. The number of NNK-induced mutations was, in fact, found to be considerably reduced by Yamabudo juice or DBQ. Yamabudo thus mitigated lung cancer by repairing the DNA damage caused by toxins. Lastly, the team also assessed biological pathways which typically help cancer cells proliferate. While all such pathways were active in the lung cancer cells, treatment with Yamabudo showed a dampening of these cancer-facilitating signals. “Stimulation of repair of alkyl DNA adducts and suppressed growth signaling pathways are potential anti-tumorigenic targets of Yamabudo juice and DBQ in NNK-induced lung tumorigenesis,” conclude the researchers. Given the broad range of tumor-suppressing properties Yamabudo displays, it is one herbal medicine that should be explored further in lung cancer research. Background Yamabudo: Vitis coignetiae Pulliat, also known as crimson glory vine or “Yamabudo” in Japan, is a berry-producing vine that grows primarily in East Asia. The juice extracted from Yamabudo berries comprises several chemical compounds that have medicinal properties. While its protective properties against skin cancer have briefly been shown before, this is the first study that explores the potential of Yamabudo in lung cancer. DNA methylation: DNA methylation is a natural chemical process intended to regulate proper functioning of our genes. A chemical group known as the “methyl” group is usually bound onto specific regions of the DNA as a mechanism to prevent genes from being turned on when not in use. However, certain toxins and other external factors can also induce DNA methylation which sometimes prevents important genes (such as those that suppress cancer) from being active. Unfortunately, the methylated forms of DNA are passed on when cells replicate. DNA methylation thereby also abets the spread of cancer. Controlling DNA methylation is an important strategy in keeping certain cancers in check. Vitamin D may protect against young-onset colorectal cancer Dana Farber Cancer Institute, August 17, 2021 Consuming higher amounts of Vitamin D – mainly from dietary sources – may help protect against developing young-onset colorectal cancer or precancerous colon polyps, according to the first study to show such an association. The study, recently published online in the journal Gastroenterology, by scientists from Dana-Farber Cancer Institute, the Harvard T.H. Chan School of Public Health, and other institutions, could potentially lead to recommendations for higher vitamin D intake as an inexpensive complement to screening tests as a colorectal cancer prevention strategy for adults younger than age 50. While the overall incidence of colorectal cancer has been declining, cases have been increasing in younger adults – a worrisome trend that has yet to be explained. The authors of the study, including senior co-authors Kimmie Ng, MD, MPH, of Dana-Farber, and Edward Giovannucci, MD, DSc., of the T.H. Chan School, noted that vitamin D intake from food sources such as fish, mushrooms, eggs, and milk has decreased in the past several decades. There is growing evidence of an association between vitamin D and risk of colorectal cancer mortality. However, prior to the current study, no research has examined whether total vitamin D intake is associated with the risk of young-onset colorectal cancer. “Vitamin D has known activity against colorectal cancer in laboratory studies. Because vitamin D deficiency has been steadily increasing over the past few years, we wondered whether this could be contributing to the rising rates of colorectal cancer in young individuals,” said Ng, director of the Young-Onset Colorectal Cancer Center at Dana-Farber. “We found that total vitamin D intake of 300 IU per day or more – roughly equivalent to three 8-oz. glasses of milk – was associated with an approximately 50% lower risk of developing young-onset colorectal cancer.” The results of the study were obtained by calculating the total vitamin D intake – both from dietary sources and supplements – of 94,205 women participating in the Nurses' Health Study II (NHS II). This study is a prospective cohort study of nurses aged 25 to 42 years that began in 1989. The women are followed every two years by questionnaires on demographics, diet and lifestyle factors, and medical and other health-related information. The researchers focused on a primary endpoint – young-onset colorectal cancer, diagnosed before 50 years of age. They also asked on a follow-up questionnaire whether they had had a colonoscopy or sigmoidoscopy where colorectal polyps (which may be precursors to colorectal cancer) were found. During the period from 1991 to 2015 the researchers documented 111 cases of young-onset colorectal cancer and 3,317 colorectal polyps. Analysis showed that higher total vitamin D intake was associated with a significantly reduced risk of early-onset colorectal cancer. The same link was found between higher vitamin D intake and risk of colon polyps detected before age 50.  The association was stronger for dietary vitamin D – principally from dairy products – than from vitamin D supplements. The study authors said that finding could be due to chance or to unknown factors that are not yet understood. Interestingly, the researchers didn't find a significant association between total vitamin D intake and risk of colorectal cancer diagnosed after age 50. The findings were not able to explain this inconsistency, and the scientists said further research in a larger sample is necessary to determine if the protective effect of vitamin D is actually stronger in young-onset colorectal cancer. In any case, the investigators concluded that higher total vitamin D intake is associated with decreased risks of young-onset colorectal cancer and precursors (polyps). “Our results further support that vitamin D may be important in younger adults for health and possibly colorectal cancer prevention,” said Ng. “It is critical to understand the risk factors that are associated with young-onset colorectal cancer so that we can make informed recommendations about diet and lifestyle, as well as identify high risk individuals to target for earlier screening.” The study was funded by grants from the U.S. National Institutes of Health and the Department of Defense; by the American Cancer Society Mentored Research Scholar Grant; and by the Project P Fund. Ng's disclosures include research funding from Pharmavite, Revolution Medicines, Janssen, and Evergrande Group; Advisory boards for Array Biopharma, Seattle Genetics, and BiomX; and consulting for X-Biotix Therapeutics. Lack of exercise and poor nutrition could increase the risk of diseases like dementia Kings College London, August 17, 2021 New research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King's College London has found that both diet and exercise can influence the risk of cognitive decline (CD) and dementia by potentially influencing hippocampal neurogenesis (the process by which the brain produces new brain cells) long before their onset. The study, published in Alzheimer's & Dementia: The Journal of the Alzheimer's Association, suggests that altered neurogenesis in the brain could potentially represent an early biomarker for both CD and dementia. The investigation studied how the blood of participants with and without CD and dementia could influence hippocampal neurogenesis in laboratory settings and whether diet and exercise were important factors. Specifically, blood samples of 418 French adults over the age of 65 were collected 12-years prior to CD and dementia diagnosis and tested on human hippocampal stems cells. Additionally, information on each participant's sociodemographic, lifestyle, and clinical data were collected and incidence cognition status and dementia were measured every 2 to 3 years over a 12-year period. Over the course of the study, the researchers established that 12 years prior to diagnosis, both CD and Alzheimer's were associated with levels of neural stem cell death. The team also found that exercise, nutrition, vitamin D levels, carotenoid and lipid levels are all associated with the rate at which cells die off. Furthermore, physical activity and nutrition were key factors that then also determined CD status.  Specifically, researchers found that reduced physical activity and increased malnutrition both increased cell death which in turn increased the risk for future CD. While previous studies have established that diet and exercise have some protective effects against CD and dementia, these roles have been poorly understood at the neurobiological level. To date, studies on animals have shown how diet and exercise can directly influence hippocampal neurogenesis, potentially explaining how exercise and diet may biologically exert their effects, but this study sheds further light on this in the context of a human model. Doctor Sandrine Thuret, the study's lead investigator from King's IoPPN said “Our study has demonstrated not only that there are individual markers of hippocampal neurogenesis associated with CD and dementia 12 years later, but also that there is some degree of specificity with respect to diagnoses of dementia subtypes. “Specifically, if an individual displays an increase in their levels of cell death during differentiation (when neural stem cells are becoming neurons), we can look at this as a potential warning sign of CD. Conversely, a decrease in levels of cell death during proliferation (the process by which a single cell divides into a pair) and reduced hippocampal progenitor cell integrity could be viewed as a predictor for Alzheimer's Disease and Vascular dementia, respectively.” According to Alzheimer's Research UK, there were a total of 525,315 people living with a dementia diagnosis in the UK in 2020[1]. Rates of cognitive decline and dementia are expected to triple in prevalence by 2040. Dr Andrea du Preez, the study's first author from King's IoPPN said, “While more work is undoubtedly needed to fully understand how diet and exercise might modulate hippocampal neurogenesis, our findings may represent an effective early preventative strategy against CD and dementia.” Acupuncture improves symptoms of chronic prostatitis/chronic pelvic pain syndrome compared to sham treatment China Academy of Chinese Medical Sciences, August 17, 2021  A multicenter randomized trial showed that 20 sessions of acupuncture over 8 weeks resulted in greater improvement in symptoms of moderate to severe chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) compared with sham therapy. Treatment effects endured over 24 weeks follow up. The findings are published in Annals of Internal Medicine. CP/CPPS manifests discomfort or pain in the pelvic region for at least 3 of the previous 6 months without evidence of infection. Lower urinary tract symptoms, psychological issues, and sexual dysfunction may also be involved. Men with CP/CPPS may have a poor quality of life due to the many neuropsychophysiologic pathophysiology factors associated with the disorder, such as inflammation in the prostate, anxiety and stress, and dyssynergic voiding. Antibiotics, a-blockers, and anti-inflammatories are the mainstays of treatment in clinical practice, but they have limited effectiveness and are associated with adverse events with long-term use. Acupuncture has shown promise as an alternative treatment, but high-quality evidence is scarce. Researchers from the China Academy of Chinese Medical Sciences randomly assigned 440 male participants (220 in each group) to either 8 weeks of acupuncture or sham therapy to assess the long-term efficacy of acupuncture for improving symptoms of CP/CPPS. The treatment was considered effective if participants achieved a clinically important reduction of at least 6 points from baseline on the National Institutes of Health Chronic Prostatitis Symptom Index at weeks 8 and 32. Ascertainment of sustained efficacy required the between-group difference to be statistically significant at both time points. The researchers found that compared with the sham acupuncture group, larger proportions of participants in the acupuncture group reported marked or moderate improvements in symptoms at all assessment points. No significant difference was found in changes in International Index of Erectile Function 5 score at all assessment time points or in peak and average urinary flow rates at week 8. No serious adverse events were reported in either group. According to the researchers, these findings show long-term efficacy of acupuncture and provide high-quality evidence for clinical practice and guideline recommendations. Eicosapentaenoic acid (EPA) decreases amyloid beta-induced neurotoxicity by decreasing neuroinflammation through regulation of microglial polarization Yunnan University (CHina), August 16, 2021 According to news reporting originating in Yunnan, People's Republic of China, research stated, “Although the cause of Alzheimer's disease (AD) is still controversial, it is generally accepted that neuroinflammation plays a key role in AD pathogenesis. Thus, regulating the polarization of microglia will help in recovering from AD since microglia can be polarized into classical M1 and alternative M2 phenotypes, M1 microglia leading to neuroinflammation and M2 microglia acting as anti-inflammatory effectors.” Financial support for this research came from National Natural Science Foundation of China (NSFC). The news reporters obtained a quote from the research from Yunnan University, “Our previous study demonstrated that eicosapentaenoic acid (EPA), an essential n-3 polyunsaturated fatty acid, may modulate glial cell activity and functions, but it is not clear whether EPA plays a role in microglial polarization. Here, we aimed to test the hypothesis that EPA may regulate the polarization of microglia and subsequently alleviate neuroinflammation and neuronal damage. Male C57BL/6 mice were fed an EPA -supplemented diet or a palm oil -supplemented diet for 42 days. On day 28 of diet feeding, the mice received a single intracerebroventricular injection of beta-peptide fragment 1-42(A beta(1-42)) or saline. The polarization of M1 and M2 microglia was evaluated by western blot using the respective markers. Changes in inflammatory cytokine mRNA levels were examined using real-time PCR. Neurological deficits were analysed using the Morris water maze and TdT-mediated dUTP Nick-End Labeling (TUNEL) assays. EPA supplementation effectively reversed the increasing trend of M1 microglial markers and the decreased expression of M2 microglial markers in the hippocampus mediated by A beta(1-42) and normalized the A beta-induced upregulation of proinflammatory cytokines and the downregulation of anti-inflammatory factors. Consistent with these findings, EPA significantly improved cognitive function and inhibited apoptotic neuronal death in the hippocampus.” According to the news reporters, the research concluded: “These results demonstrated that EPA appears to have potential effects on regulating microglial polarization, which contributes to alleviating neuroinflammation and may have beneficial effects for preventing and treating AD.” This research has been peer-reviewed. Yoga and meditation improve mind-body health and stress resilience University of Southern California  August 19, 2021  Many people report positive health effects from practicing yoga and meditation, and experience both mental and physical benefits from these practices. However, we still have much to learn about how exactly these practices affect mind-body health. A new research article published in Frontiers in Human Neuroscience investigates the effects of yoga and meditation on brain derived neurotrophic factor (BDNF), the activity on the hypothalamic pituitary adrenal (HPA) effects and inflammatory markers. By studying the participants of an intensive 3-month yoga and meditation retreat, the researchers found that the practices positively impacted BDNF signaling, the cortisol awakening response (CAR) and immunological markers, and in addition improved subjective wellbeing. In this study, the retreat participants were assessed before and after participating in a 3-month yoga and meditation retreat that involved daily meditation and Isha yoga, accompanied by a vegetarian diet. The yogic practices consisted of physical postures, controlled breathing practices, and seated meditations during which the participants focused on mantra repetition, breath, emptying the mind and bodily sensation. The researchers measured psychometric measures, brain derived neurotrophic factor (BDNF), circadian salivary cortisol levels, as well as pro- and anti-inflammatory cytokines. They also collected data on psychometric variables including mindfulness, absorption, depression and anxiety, and investigated the relationship between psychological improvements and biological changes. The data showed that participation in the retreat was associated with decreases in both self-reported anxiety and depression as well as increases in mindfulness. The research team observed increases in the plasma levels of BDNF, a neuromodulator that plays an important role in learning, memory and the regulation of complex processes such as inflammation, immunity, mood regulation, stress response and metabolism. They also observed increases in the magnitude of the cortisol awakening response (CAR) which is part of the hypothalamic pituitary adrenal axis (HPA), suggesting improved stress resilience. Moreover, there was a decrease in inflammatory processes caused by an increase of the anti-inflammatory cytokine Interleukin-10 and a reduction of the pro-inflammatory cytokine Interleukin-12 after the retreat. "It is likely that at least some of the significant improvements in both HPA axis functioning as exemplified by the CAR as well as neuroimmunologic functioning as exemplified by increases in BDNF levels and alterations in cytokines were due to the intensive meditation practice involved in this retreat," says corresponding author Dr Baruch Rael Cahn (University of Southern California, USA). The research team hypothesize that the pattern of biological findings observed in their study is linked to enhanced resilience and wellbeing. "The observed increased BDNF signaling possibly related to enhanced neurogenesis and/or neuroplasticity, increased CAR likely related to enhanced alertness and readiness for mind-body engagement, and increased anti- and pro-inflammatory cytokines possibly indicating enhanced immunological readiness," explains Dr Cahn. "An intriguing possible link between the effects on BDNF and the CAR is hippocampal functional integrity, since increased BDNF levels due to physical exercise has previously been shown to relate with hippocampal neurogenesis and likely relate to its positive effects on well-being and depression." In the light of previous studies of the positive effects of meditation on mental fitness, autonomic homeostasis and inflammatory status, the researchers think that their findings are related to the meditative practices that the retreat participants engaged in. However, they suggest that some of the observed changes may also be related to the physical aspects of the retreat - yoga practice and diet - and that the observed change patterns are a reflection of wellbeing and mind-body integration. The next step will be to conduct further research in order to clarify the extent to which the positive changes on mind-body wellness and stress resilience are related to the yoga and meditation practices respectively, and to account for other possible contextual factors such as social dynamics, diet and the impact of the teacher. "To our knowledge, our study is the first to examine a broad range of pro- and anti-inflammatory markers in a healthy population before and after a yoga-meditation intervention. Our findings justify further studies of yoga and meditation retreats assessing for the replicability, specificity and long-term implications of these findings," concludes Dr Cahn.  

This week we discuss the Minnesota National Guard’s Covid 19 training and response, learn about the Minnesota Department of Veterans Affairs Covid 19 Relief and get an update from the Minnesota Patriot Guard. Guests include: Col. Scott Rohweder – Minnesota … Continue reading → The post MNNG and MDVA Covid-19 Relief and Response appeared first on Minnesota Military Radio.

This week we talk about the Diversity & Inclusion Initiative at the Minnesota National Guard, meet with the Claims & Outreach Director at the Minnesota Department of Veterans Affairs and get a update from the Minnesota Association of County Veterans … Continue reading → The post Diversity & Inclusion at the MNNG and Claims & Outreach at MDVA appeared first on Minnesota Military Radio.

Neben den anerkannten Risikofaktoren Alkohol und Rauchen gewinnt die individuelle Suszeptibilität, als zusätzlicher Risikofaktor für die Entwicklung von Kopf-Hals-Tumoren zunehmend an Bedeutung. Eine genetische Disposition zur DNA-Instabilität oder präformierte Defizite im Bereiche der DNA-Reparaturmechanismen begünstigen das Auftreten und die Persistenz kritischer Mutationen. Durch diese „endogenen“ Risikofaktoren wird eine Tumorenstehung begünstigt, so dass manche Personen, bei gleicher Expositionsstärke und -dauer gegenüber exogenen kanzerogenen Einflüssen, leichter ein Karzinom entwickeln, als andere. In der vorliegenden Arbeit sollte untersucht werden, ob Unterschiede in der Mutagensensitivität und/oder der DNA-Reparaturkapazität zwischen einer Versuchsgruppe aus Patienten mit einem Karzinom des oberen Aerodigestivtraktes und einer gesunden Probantengruppe feststellbar sind. Die beiden Gruppen wurden nach Geschlecht, Alter, Tabak- und Alkoholkonsum abgeglichen. Das Kollektiv der Karzinompatienten umfasste 20 Personen, die an einem oropharyngealen Karzinom erkrankt waren. Der Kontrollgruppe gehörten ebenfalls 20 Personen an, die jedoch alle frei von einem Tumorleiden waren. Perioperativ wurden zur Testung jeweils 20 Schleimhautproben gewonnen. an Lymphozyten standen aus beiden Gruppen jeweils 15 Proben zur Verfügung. Die anerkannt karzinogenen Inhaltsstoffe des Tabakrauchs Benzo[a]pyren, BPDE, NDEA, NNN, NNK, NDEA wurden als Testsubstanzen verwendet, um Schäden an der DNA zu induzieren. MNNG und die Lösungssubstanz DMSO dienten als Positiv- und Negativkontrolle. Schleimhautzellen und Lymphozyten wurden jeweils für 60 Minuten mit den genannten Fremdstoffen inkubiert. Der Reparaturversuch wurde ausschließlich mit NDEA durchgeführt. Nach Auswaschung des Fremdstoffes wurde den Schleimhautzellen 15 und 30 Minuten und den Lymphozyten 15, 30 und 60 Minuten Zeit zur Reparatur entstandener DNA-Schäden gewährt. Zur quantitativen Darstellung der fremdstoffinduzierten DNA-Schädigungen und Reparaturleistung wurde der Comet Assay benutzt. Alle getesteten Substanzen zeigten im Vergleich zur Kontrollsubstanz DMSO ein signifikantes Schädigungsniveau. Die Ergebnisse der Versuche zur Mutagensensitivität zeigten eine signifikant höhere Schädigung der Schleimhautzellen der Tumorgruppe durch NNN. In den weiteren Versuchen zur Mutagensensitivität konnte durch keine weitere Substanz, weder in Schleimhautzellen, noch in Lymphozyten, eine Schädigung ausgelöst werden, die einen signifikanten Unterschied zwischen Tumor- und Kontrollgruppe aufzeigt. Für Schleimhautzellen und Lymphozyten konnte ein Ansteigen der DRC im zeitlichen Verlauf von 0 bis 30, bzw. 0 bis 60 Minuten erfasst werden. Ein signifikanter Unterschied zwischen Versuchs- und Kontrollgruppe bestand nicht. Alle benutzen Testsubstanzen verursachen nachweisbare DNA-Schäden in unterschiedlicher Stärke und Homogenität. Sowohl in Lymphozyten, als auch Epithelzellen fand unter den eingesetzten In-vitro-Bedingungen eine zeitabhängige zunehmende Reparatur der geschädigten DNA statt. In der statistischen Auswertung der Ergebnisse konnte ausschließlich für das Agens NNN (p = 0,04) eine erhöhte Sensitivität der Schleimhautzellen von Karzinompatienten nachgewiesen werden. Zur Bestätigung dieses Ergebnisses müssen weitere Versuche folgen. Insgesamt ließ sich die Hypothese einer unterschiedlichen Mutagensensitivität und DNA-Reparaturkapazität beim Vergleich von Patienten mit einem Karzinom des Kopf-Hals-Bereiches und in der Population der vorliegenden Arbeit nicht bestätigen.

Die Schleimhaut des nasalen Raums stellt das primäre Kontaktorgan für inhalierte Stoffe dar. Um den Körper vor toxischen Wirkungen zu schützen und den Geruchssinn zu unterstützen, besitzen die Epithelzellen der respiratorischen Anteile erhebliche metabolische Kompetenz. Interindividuelle Unterschiede im Fremdstoffmetabolismus können in Verbindung mit einer beruflichen Exposition gegenüber inhalativen Karzinogenen zur Entstehung von Malignomen des sinonasalen Raums führen. Um gefährliche Stoffe und gefährdete Populationen anhand von in-vitro-Versuchen identifizieren zu können, wurde ein dreidimensionales Kultursystem humaner nasaler Mukosa vorgestellt, das die Verhältnisse in vivo möglichst realistisch abbildet. Dazu wurden Resektate humaner nasaler Mukosa in 1 mm3 großen Fragmenten unter optimierten Umweltbedingungen kultiviert. Innerhalb einer Woche bildeten sich daraus vollständig epithelisierte Miniorgane mit physiologischen histomorphologischen und funktionellen Eigenschaften. Um die Leistungsfähigkeit der Miniorgane zu evaluieren, wurden sie ein- oder mehrfach gegenüber den bekannt genotoxischen Substanzen Natriumdichromat, N-Nitrosodiethylamin (NDEA) und N-Methyl-N’-nitro-N-nitrosoguanidin (MNNG) exponiert. Parallel dazu wurden zum Vergleich Einzelzellsuspensionen mit diesen Stoffen inkubiert. Die induzierten genetischen Schäden wurden mit Hilfe der alkalischen Version des Einzelzell-Mikrogelelektrophorese-Assay quantifiziert. Der Anteil apoptotischer Vorgänge an hohen DNS-Schäden im Einzelzell-Mikrogelelektrophorese- Assay wurde durch den Annexin-V-Affinitätstest erfasst. Um den Erhalt der metabolischen Kompetenz der Zellen der Miniorgane im Verlauf der Kultivierung zu belegen, wurde die Konzentration von Cytochrom P450 2A6, einem Schlüsselenzym im Metabolismus zahlreicher inhalativer Giftstoffe, durchflusszytometrisch bestimmt. Die Miniorgane blieben über den Kulturzeitraum strukturell und funktionell intakt. Die einmalige Exposition gegenüber Natriumdichromat und MNNG verursachte erhebliche genetische Schäden, die bei wiederholter Inkubation trotz 48stündiger Reparaturphasen weiter zunahmen. Im Falle von Natriumdichromat stieg analog dazu der Anteil apoptotischer Zellen rasant an. Bei MNNG war dagegen keine erhöhte Apoptoserate nachweisbar. Die wiederholte Inkubation der Miniorganen mit NDEA ergab weder einen signifikanten genotoxischen Effekt, noch einen Anstieg der Apoptoserate, obwohl das für die Aktivierung von NDEA entscheidende Apoenzym Cytochrom P450 2A6 über den gesamten Untersuchungszeitraum in den Zellen nachgewiesen werden konnte. Im Vergleich der DNS-Fragmentierung erwiesen sich die in Suspension inkubierten Einzelzellen als empfindlicher gegenüber der Wirkung von Natriumdichromat und MNNG. Miniorgane nasaler Mukosa sind für toxikologische Studien optimal geeignet, da sie Untersuchungen an humanem Zielgewebe über einen längeren Untersuchungszeitraum erlauben. Dies eröffnet vielfältige Versuchsanordnungen hinsichtlich Expositionsfrequenz und Reparaturintervallen. Zudem erscheinen die Kulturen ausreichend robust, um zukünftig verschiedene realistische Expositionsmodelle, wie Begasungsanlagen und komplexe Mischungen, einzusetzen.

Umwelt- und Arbeitsstoffe stellen wichtige Faktoren bei der Kanzerogenese im menschlichen Körper dar. In der vorliegenden Arbeit wurden einige Vertreter von Umweltstoffen ausgewählt und auf ihre kanzerogene Wirkung hin untersucht: N-Nitrosodiethylamin (NDEA) für die Nitrosamine, Natriumdichromat (Na2Cr2O7) für die Chromverbindungen, Mono(2-Ethylhexyl)-Phthalat (MEHP) für die Phthalate und Benzo[a]pyren-Diolepoxid (BPDE) für die polyzyklischen Kohlenwasserstoffe. Als Negativkontrolle diente Dimethylsulfoxid (DMSO) und als Positivkontrolle N-Methyl-N‘-Nitro-N-Nitrosoguanidin (MNNG). Da viele dieser Stoffe über die Atemwege aufgenommen werden, ist die Schleimhaut des oberen Aerodigestivtraktes besonders exponiert. Als Untersuchungsmaterial diente deshalb humane nasale Schleimhaut. Um möglichst lebensnahe Bedingungen zu schaffen, wurden aus dieser ca. 1mm3 große Miniorgane gewonnen, die über eine Woche kultiviert wurden, was zu einer vollständigen Epithelialisierung führte. Die im natürlichen Zellverband verbliebenen Zellen konnten daraufhin mehrmals mit Fremdstoffen inkubiert werden. Die dazwischenliegenden Zeitintervalle ließen Reparaturvorgänge zu. Die Schädigungsmuster von Miniorganzellen wurden auch mit denen von Einzelzellen verglichen, die vor der Inkubation separiert worden waren. Dabei wurden sowohl Einzelzellen aus Frischbiopsaten und als auch Einzelzellen aus Miniorganen nach 7-tägiger Kultivierung getestet. Zur quantitativen Schädigungsanalyse wurde die alkalische Einzelzell-Mikrogelelektrophorese (Comet Assay) angewandt, bei der es zu einer Wanderung von gelösten DNA-Bruchstücken im elektrischen Feld kommt. Diese Wanderung konnte durch anschließende Anfärbung unter dem Fluroszenzmikroskop sichtbar gemacht werden. Die Ergebnisse zeigten unterschiedliche Fragmentierungen der DNA nach einmaliger und dreimaliger Fremdstoffinkubation: Die DNA-Schädigungen der Miniorgane blieben nach ein- und dreimaliger Inkubation mit NDEA und MEHP auf gleichem Niveau. Dagegen traten bei jeder Inkubation mit Na2Cr2O7, BPDE und MNNG zunehmende DNA-Fragmentierungen auf. Die aus Frischbiopsaten gewonnenen Einzelzellen zeigten bei jeder der getesteten Substanzen eine erhöhte Empfindlichkeit. Der direkte Vergleich zwischen Einzelzellen und Miniorganen nach 7 Tagen ergab eine gleich hohe Schädigung für NDEA. Bei den anderen getesteten Stoffen wiesen die Einzelzellen höhere DNA-Fragmentierungen auf. Es konnte gezeigt werden, dass alle getesteten Stoffe Schädigungen an der Erbsubstanz in Form von Einzelstrangbrüchen hervorrufen. Im Vergleich zwischen Miniorganen und Einzelzellen wiesen Einzelzellen überwiegend eine höhere Empfindlichkeit gegenüber Fremdstoffen auf als die im epithelialen Strukturverband belassenen Zellen der Miniorgane. Das Miniorganmodell bot mehrfache Inkubationsmöglichkeiten und ließ so Reparaturphasen zu. Durch die Verwendung von Miniorgankulturen können lebensnahe Bedingungen geschaffen werden, die die Vorgänge im menschlichen Körper besser widerspiegeln als ein Einzelzellmodell. Die Verwendung von Miniorgankulturen eignet sich somit zur Untersuchung der metabolischen Kompetenz von Zellen und der DNA-Reparaturmechanismen. Dadurch kann die hier vorgestellte Methode zur Prävention von malignen Tumoren des oberen Aerodigestivtraktes einen wichtigen Beitrag leisten. Auch die hier erstmals in Verbindung mit Miniorganen eingesetzte alkalische Einzelzell-Mikrogelelektrophorese (Comet Assay) erwies sich als geeigneter Kurzzeittest zur Schädigungsanalyse. Das gezeigte Modell ermöglicht die Weiterentwicklung einer Screeningmethode für die Genotoxizität von Umweltstoffen unter Berücksichtigung individueller Empfindlichkeiten.

Genotoxic effects of xenobiotics are a possible step in tumor initiation in the mucosa of the upper aerodigestive tract. Using the comet assay, detecting genotoxicity in human tissue has been restricted to single incubations in vitro, but in vivo most xenobiotics harm their target in a repetitive or chronic manner. Therefore, we propose a model, which provides repetitive incubations in human upper aerodigestive tract mucosa cultures. Samples of human inferior nasal turbinate mucosa (n = 25) were cultured according to a modified version of a technique originally described by Steinsvag. On day 1 fresh samples and on days 7, 9 and 11 organ cultures were incubated with N-nitrosodiethylamine (NDEA), sodium dichromate (Na2Cr2O7) and N'-methyl-N-nitro-N-nitrosoguanidine(MNNG). Mucosa samples and organ cultures, respectively, underwent a modified comet assay on days 1, 7 and 11. Genotoxicity could be shown for NDEA, Na2Cr2O7 and MNNG on days 1, 7 and 11. Duration of tissue culture and repetitive incubations did not significantly influence the results for NDEA. Nevertheless, Na2Cr2O7 and MNNG caused higher genotoxic effects on cultures subjected to the comet assay on day 11. This model may help to assess genotoxic hazards posed by environ mental pollutants that have a cumulative character in repetitive or chronic exposure in vivo. Copyright (C) 2001 S. Karger AG, Basel.