Metabolism of mutagens and carcinogens in woodchuck liver and its relationship with hepatitis virus infection

• Published in: Cancer research (Chicago, Ill.) Ill.), 1987-08, Vol.47 (15), p.4052-4058
• Main Authors: DE FLORA, S, CAMOIRANO, A, ROMANO, M, ASTENGO, M, CESARONE, C. F, MILLMAN, I
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Biotransformation; Carcinogens - metabolism; Cell metabolism, cell oxidation; Cell physiology; Cocarcinogenesis; Female; Fundamental and applied biological sciences. Psychology; Hepatitis Viruses - isolation & purification; Hepatitis, Viral, Animal - metabolism; Liver - metabolism; Liver - pathology; Liver Neoplasms - etiology; Liver Neoplasms - veterinary; Male; Marmota - metabolism; Marmota - microbiology; Mice; Molecular and cellular biology; Mutagens - metabolism; Rats; Rats, Inbred Strains; Rodent Diseases - metabolism; Sciuridae - metabolism; Species Specificity
• ISSN: 0008-5472; 1538-7445

Thirty-six wild-caught woodchucks (Marmota monax) were characterized 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 hydrocarbon hydroxylase, glutathione, cytosolic enzymes involved in its metabolism (glutathione S-transferase, glutathione peroxidase, and glutathione reductase), in the hexose monophosphate shunt (glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase), NADH- and 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 B1, 2-aminofluorene, and trans-7,8-dihydrobenzo(a)pyrene] to mutagenic metabolites in the Ames reversion test and to decrease the activity of direct-acting mutagens [i.e., 4-nitroquinoline N-oxide, 2-methoxy-6-chloro-9-[3-(2-chloroethyl)aminopropylamino]acridine X 2HCl, and sodium dichromate]. A considerable interindividual variability in metabolism was observed among the examined woodchucks. Some of the investigated parameters 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 reductase 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 detoxification mechanisms are more efficient in rats and mice.