Enhanced generation of carcinogenic DNA lesions in rats fed a high fat choline, methionine deficient diet

Abstract

Aims: Obese insulin deficient, Leptin deficient Zucker rats (fa/fa) develop spontaneously metabolic syndrome and fatty liver. It has been shown that obese Zucker rats exhibited increased hepatic oxidative stress and showed a significant increase in carcinogenic exocyclic etheno-DNA adducts as compared to their lean littermates (Wang et al., Hepatology 50,453: 2009). Therefore, we wondered whether such an effect could also be observed in an animal model in which steatosis is induced by diets and which resembles better the human situation. Methods: In the present study male Wistar rats received a semi-synthetic high-fat, choline, methionine deficient (HFCMD) diet. After ten weeks of feeding the animals were killed. Rats with the HFCMD diet developed fatty liver with inflammation. In the serum ALT, AST, Cholesterol, tumor necrosis factor a (TNFα), Adiponectin and Leptin were determined. In the liver Cholesterol and Triglyceride were measured and in addition exocyclic etheno-DNA adducts were immunohistologically determined. Results: The HFCMD diet results in a significant increase of ALT- and AST-activity, and of TNFα, while serum Adiponectin and Leptin were found to be significantly decreased. In addition significant increased levels of carcinogenic exocyclic etheno-DNA adducts were also detected in the livers of the rats with the HFCMD diet as compared to their controls. Conclusions: Nonalcoholic fatty liver induced by HFCMD diets is associated with an increased level of carcinogenic DNA adducts deriving from oxidative stress. This may explain at least in part the carcinogenic potential of this liver disease.