Relationship with Hepatitis Virus Infection Metabolism of Mutagens and Carcinogens in Woodchuck Liver

Thirty-six wild-caught woodchucks (Marmota monax) were charac terized according to sex, weight, trapping locality, liver pathology, and serum or hepatic markers of woodchuck hepatitis virus. Liver subcellular fractions were assayed for microsomal cytochromes P-450, aryl hydro carbon hydroxylase, glutathione, cytosolic enzymes involved in its metab olism (glutathione S-transferase, glutathione peroxidase, and glutathione reducÃ-ase), in the hexose monophosphate shunt (glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase), NADHand NADPH-dependent diaphorases, and DT diaphorase. Moreover, liver postmitochondrial fractions were assayed for their ability to activate procarcinogens (i.e., a tryptophan pyrolysate product, aflatoxin B,, 2aminofluorene, and fra/w-7,8-dihydrobenzo(fl)pyrene| to mutagenic me tabolites in the Ames reversion test and to decrease the activity of directacting mutagens (i.e., 4-nitroquinoline /V-oxide, 2-methoxy-6-chloro-9-[3(2-chloroethyl)aminopropylamino]acridine • 2HC1, and sodium dichrontate|. A considerable interindividual variability in metabolism was ob served among the examined woodchucks. Some of the investigated pa rameters were more elevated in virus carriers, especially in those suffering from chronic active hepatitis, but only a few of the recorded differences (i.e., oxidized glutathione reducÃ-ase and NADPH-dependent diaphorase) were statistically significant. The comparison of the monitored activities in woodchucks and in other rodent species (rat and mouse) led to the conclusion that the liver metabolism of mutagens and carcinogens in woodchucks is more oriented in the sense of activation, while detoxifi cation mechanisms are more efficient in rats and mice.