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Effect of Dietary Restriction on DNA-Adduct Formation of Benzo[a]pyrene and 2-Acetylaminofluorene in Mouse Liver
Authors:Ming W. Chou  Wen Chen  Jasyl Nichols  Marina Mikhailova  Ronald W. Hart
Affiliation:National Center for Toxicological Research , Jefferson, Arkansas, USA
Abstract:Dietary restriction (DR) alters hepatic drug metabolizing enzyme activities that affect the metabolic activation of xenobiotics. Previously, we have studied the effect of DR on the formation of benzo[a]pyrene (BaP)-DNA adducts in male Fischer 344 rats. In this study, the effects of DR on the formation of specific BaP-DNA adducts in mouse livers were investigated. In addition, 2-acetylaminofluorene (2-AAF) modified DNA adducts in livers of mice and rats were also examined. DR reduced the body and liver weights of male B6C3F1 mice. Both the total [3H]BaP-DNA binding and the specific BaP-DNA adduct, N2-dG-BaP, detected by 32P-postlabeling technique, were found to be greater in DR mice than in animals fed al libitum (AL). The formation of the 2-AAF-DNA adduct, AF-C8-dG, was not affected by DR. Similar results were obtained from the in vitro DNA adduct formation of these two carcinogens mediated by rat and mouse liver microsomes. The effect of DR on the formation of BaP- and 2-AAF-modified DNA adducts is discussed.
Keywords:Dietary restriction  benzo[a]pyrene  2-acetylaminofluorene  BaP-DNA adduct  2-AAF-DNA adduct  DNA strand breaks
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