METABOLIC-ACTIVATION OF AFLATOXIN B-1 TO AFLATOXIN B-1-8,9-EPOXIDE INWOODCHUCKS UNDERGOING CHRONIC ACTIVE HEPATITIS

Chronic hepatitis B virus infection as well as consumption of food con taminated with the mycotoxin aflatoxin B-1 are considered to be 2 majo r risk factors for the development of primary liver cancer in humans, Furthermore, epidemiological surveys indicate that hepatitis B virus a nd aflatoxin B-1 might act synergistically to induce primary liver can cer. In the present study, we have tested the hypothesis that the meta bolic activation of aflatoxin B-1 to aflatoxin B-1-8,9-epoxide, the ul timate mutagenic and carcinogenic mycotoxin metabolite, is enhanced in an experimental model of chronic hepatitis using woodchucks, chronica lly infected with the woodchuck hepatitis virus. Woodchuck liver micro somes were incubated with radiolabeled aflatoxin B-1, the resulting af latoxin B-1-8,9-epoxide was trapped as a glutathione conjugate and its formation rate was determined by a reversed-phase HPLC analysis. In w oodchuck hepatitis virus-positive woodchucks, activation of aflatoxin B-1 to aflatoxin B-1-8,9-epoxide was reduced when compared to woodchuc k hepatitis virus-free animals, and the extent of the reduction was de pendent on the severity of the hepatitis, Hence, at least in woodchuck s, a chronic hepadnaviral infection does not lead to an enhanced activ ation of aflatoxin B-1. (C) 1997 Wiley-Liss, Inc.