COMPARATIVE GASTROINTESTINAL ENZYME-ACTIVITY AND ACTIVATION OF THE PROMUTAGEN 2,6-DINITROTOLUENE IN MALE CD-1 MICE AND MALE FISCHER-344 RATS

Comparative intestinal nitroreductase, azo reductase, β-glucuronidase, dechlorinase and dehydrochlorinase activities in young male Fischer 344 rats and young male CD-1 mice were measured in vitro while the comparative biotransformation of 2,6-dinitrotoluene to mutagenic metabolites was determined in vivo. The mice, which exhibit a high spontaneous incidence of hepatomas, had markedly greater nitroreductase activity and metabolized significantly more 2,6-dinitrotoluene to mutagenic metabolites than did Fischer 344 rats, which show a low incidence of liver tumors. Results of this study indicate that species differences in the incidence of hepatomas may be influenced by microbial flora and/or the biotransformation of xenobiotics in the G.I. tract. © 1990.