[Inhibitory effect of ortho-aminoazotoluene on diethylnirtosamine hepatocarcinogenesis in suckling mice. Phenomenon and possible mechanism].

The modifying effect of the one compound on carcinogenicity of the other in the combined application is attributed usually to some changes in the carcinogen metabolism, i.e. its activation or inactivation.

[Increase of general toxic effects and decrease of hepatocarcinogenic effects of diethylnitrosamine administered to mice in conjunction with isopropanol].

It is considered that diethylnitrosamine (DENA) is metabolized mostly in the liver with producing highly reactive compounds alkylating cellular macromolecules and causing toxic and carcinogenic effects. However, competitive inhibition of cytochrome P450 2E1, which metabolizes DENA, by its other substrate, isopropanol, does not weaken, but enhances the toxicity of DENA effect on mice and reduces the number of preneoplastic nodules and liver tumors induced by it. In short-term tests for mutagenicity (in the Ames test and the SOS-hromotest) DENA causes moderate damage of DNA that reduces liver microsomal enzymes, that metabolize nitrosamines.

[Expression of nuclear hormone receptors PPAR, LXR and RXR in the liver and lipid and glucose levels in blood in susceptible and resistant to hepatocarcinogenesis mice strains].

Earlier it was shown that male mice of the DD/He strain were highly susceptible to ortho-aminoasotoluene (OAT) induced hepatocarcinogenesis, and resistant to spontaneous liver tumor development as compared to the CC57BR/Mv strain. In the present work we have made a comparative investigation of peroxisome proliferator-activated receptor (PPAR), liver X-receptor (LXR) and retinoic X-receptor (RXR) mRNA levels in liver as well as concentrations of corticosterone, glucose, lipids and insulin in blood of male DD/He and CC57BR/Mv mice. Using the multiplex RT-PCR method it was found that PPAR-alpha, PPAR-gamma, RXR-alpha and RXR-beta mRNA content was essentially decreased in the liver of DD mice as compared to mice of the CC57BR strain.

[O-aminoazotoluene inhibits DENA-induced hepatocarcinogenesis when used together in mice].

When used separately, diethylnitrosamine (DENA) initiates 4-6 times more neoplastic lesions in the liver of suckling mice than ortho-aminoazotoluene (OAT) lower. However, after combined treatment with either carcinogen the total number of hepatic lesions was significantly than that in mice injected with DENA only. Similar inhibition of DENA-induced hepatocarcinogenesis was observed when OAT was administered 8-12 hrs after DENA.

[Effect of hepatocarcinogenicity of estragole on the glucocorticoid-mediated induction of liver-specific enzymes and the activity of the transcription factors FOXA and HNF4 in the liver of mouse and rat].

The carcinogenic effects of estragole in mice of the earlier unexplored strain ICR has been studied. It has been shown that there is a distinct correlation between the extent of inhibition of glucocorticoid-mediated induction of tyrosine aminotransferase and trypthophan oxygenase after acute administration of estragole and the frequency of liver tumors after estragole exposure. Estragole inhibits the induction of these enzymes only in female mice, but not in male mice and rats.