title: Metabolic activation of aflatoxin B1 to aflatoxin B1-8,9-epoxide in woodchucks undergoing chronic active hepatitis.
abstract: Chronic hepatitis B virus infection as well as consumption of food contaminated with the mycotoxin aflatoxin B1 are considered to be 2 major risk factors for the development of primary liver cancer in humans. Furthermore, epidemiological surveys indicate that hepatitis B virus and aflatoxin B1 might act synergistically to induce primary liver cancer. In the present study, we have tested the hypothesis that the metabolic activation of aflatoxin B1 to aflatoxin B1-8,9-epoxide, the ultimate mutagenic and carcinogenic mycotoxin metabolite, is enhanced in an experimental model of chronic hepatitis using woodchucks, chronically infected with the woodchuck hepatitis virus. Woodchuck liver microsomes were incubated with radiolabeled aflatoxin B1, the resulting aflatoxin B1-8,9-epoxide was trapped as a glutathione conjugate and its formation rate was determined by a reversed-phase HPLC analysis. In woodchuck hepatitis virus-positive woodchucks, activation of aflatoxin B1 to aflatoxin B1-8,9-epoxide was reduced when compared to woodchuck hepatitis virus-free animals, and the extent of the reduction was dependent on the severity of the hepatitis. Hence, at least in woodchucks, a chronic hepadnaviral infection does not lead to an enhanced activation of aflatoxin B1.
authors.affiliation: Institute of Toxicology, University of Mainz, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Gemechu-Hatewu
authors.forename: K L
authors.initials: KL
authors.lastname: Platt
authors.forename: F
authors.initials: F
authors.lastname: Oesch
authors.forename: H J
authors.initials: HJ
authors.lastname: Hacker
authors.forename: P
authors.initials: P
authors.lastname: Bannasch
authors.forename: P
authors.initials: P
authors.lastname: Steinberg
mesh_terms: D016604:Aflatoxin B1 / Q000031:analogs & derivatives* / Q000378:metabolism*; D000818:Animals; D005260:Female; D017919:Hepatitis B Virus, Woodchuck; D019694:Hepatitis B, Chronic / Q000378:metabolism*; D006524:Hepatitis, Viral, Animal / Q000378:metabolism*; D008297:Male; D008392:Marmota; D008862:Microsomes, Liver / Q000378:metabolism*; D009153:Mutagens / Q000378:metabolism*
chemical_list: D009153:Mutagens; C074511:aflatoxin B1-8,9-dichloride; D016604:Aflatoxin B1