TY  - THES
A1  - Baumann, Klaus
T1  - Modulierende Effekte von Kaffee auf die Induktion von Mikrokernen durch mutagene Substanzen in Mauslymphomzellen L5178Y
T1  - Coffee as an effect modifier of mutagenicity in L5178Y mouse lymphoma cells treated with mutages
N2  - Kaffee, die in der westlichen Welt am häufigsten verwendete psychoaktive Substanz, erwies sich im Mikrokern-Testes an Maus-Lymphomzellen L 5178Y als modulierend auf bekannte mutagene Agentien. In dieser Arbeit wurde meist Instantkaffee verwendet, der gegen N-Methyl-N-Nitro-N-Nitrosoguanidin (MNNG), Mitomycin C (MMC), Genistein, und Methylmethansulfonat getestet wurde. Bei MMC und Genistein erwies sich Kaffee als antimutagen. Bei MNNG hatte Kaffee keinen klaren Einfluss auf die Gentoxizität, ebenso blieb die Kaffee-Wirkung bezüglich MMS unklar. Kaffee minderte dosisabhängig das Wachstum und die Überlebensrate von L 5178Y - Zellen. Es wurde die Frage nach den Ursachen der modulierenden Effekte diskutiert. Insbesondere wurde die Hypothese erörtert, dass für die Richtung der Modulation nicht so sehr die Konzentration des Kaffees, sondern die mutagene Potenz der koinkubierten Substanz eine entscheidende Rolle spielen könnte. Ggf. wirkt Kaffee - im Sinne eines "abhärtenden" Effektes - bei schwach mutagenen Substanzen anitmutagen, bei stark mutagenen Substanzen hingegen synergistisch mutagen.
N2  - Coffee, the most commonly used psychoactive substance in the western hemisphere, was regarded as an effect modifier of mutagenicity in L5178Y mouse lymphoma cells treated with mutages. Mainly instant-coffee was tested against N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), mitomycin C (MMC), genistein, und methylmethanesulfonate (MMS). Coffee was antimutagen against mitomycin C (MMC) and genistein. No clearly influence was seen against MNNG or MMS. Dose-dependent Coffee reduces the growing and survival rate of L5178Y mouse lymphoma cells. The reasons for the modifying-effects of coffee were discussed. The hypothesis was found, that the concentration of the coffee ist not so influential in making antimutagene or mutagene effects, rather the mutagen power-factor of the coincubating substances. Coffee could be an “indurating” parameter: Causing antimutage effects in the presence of “gentle” mutagens, causing synergistic mutagen or zytotoxic effects in the presence of “strong” mutagens.
KW  - Kaffee
KW  - induzierte Mutation
KW  - Coffein
KW  - Antimutagen
KW  - Mutagen
KW  - Mauslymphomtest
KW  - Mauslymphomzellen L5178Y
KW  - Mikrokerne
KW  - Effekt-Modifizierung
KW  - Janus-Aktivität
KW  - coffee
KW  - caffeine
KW  - micronuclei
KW  - mouse lymphoma cells
KW  - mutagenicity
KW  - antimutagenicity
Y1  - 2009
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-36996
ER  - 
TY  - JOUR
A1  - Bankoglu, Ezgi Eyluel
A1  - Tschopp, Oliver
A1  - Schmitt, Johannes
A1  - Burkard, Philipp
A1  - Jahn, Daniel
A1  - Geier, Andreas
A1  - Stopper, Helga
T1  - Role of PTEN in Oxidative Stress and DNA Damage in the Liver of Whole-Body Pten Haplodeficient Mice
JF  - PLoS One
N2  - Type 2 diabetes (T2DM) and obesity are frequently associated with non-alcoholic fatty liver disease (NAFLD) and with an elevated cancer incidence. The molecular mechanisms of carcinogenesis in this context are only partially understood. High blood insulin levels are typical in early T2DM and excessive insulin can cause elevated reactive oxygen species (ROS) production and genomic instability. ROS are important for various cellular functions in signaling and host defense. However, elevated ROS formation is thought to be involved in cancer induction. In the molecular events from insulin receptor binding to genomic damage, some signaling steps have been identified, pointing at the PI3K/AKT pathway. For further elucidation Phosphatase and Tensin homolog (Pten), a tumour suppressor phosphatase that plays a role in insulin signaling by negative regulation of PI3K/AKT and its downstream targets, was investigated here. Dihydroethidium (DHE) staining was used to detect ROS formation in immortalized human hepatocytes. Comet assay and micronucleus test were performed to investigate genomic damage in vitro. In liver samples, DHE staining and western blot detection of HSP70 and HO-1 were performed to evaluate oxidative stress response. DNA double strand breaks (DSBs) were detected by immunohistostaining. Inhibition of PTEN with the pharmacologic inhibitor VO-OHpic resulted in increased ROS production and genomic damage in a liver cell line. Knockdown of Pten in a mouse model yielded increased oxidative stress levels, detected by ROS levels and expression of the two stress-proteins HSP70 and HO-1 and elevated genomic damage in the liver, which was significant in mice fed with a high fat diet. We conclude that PTEN is involved in oxidative stress and genomic damage induction in vitro and that this may also explain the in vivo observations. This further supports the hypothesis that the PI3K/AKT pathway is responsible for damaging effects of high levels of insulin.
KW  - insulin
KW  - mouse models DNA damage
KW  - oxidative stress
KW  - mammalian genomics
KW  - fatty liver
KW  - micronuclei
KW  - insulin signaling
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146970
VL  - 11
IS  - 11
ER  -