Biochemical and molecular aspects of mammalian susceptibility to aflatoxin B1 carcinogenicity.
Aflatoxin B1 (AFB1) is a fungal toxin that has been implicated as a causative agent in human hepatic and extrahepatic carcinogenesis. In this review, the mechanisms involved in AFB1 toxicity are delineated, in order to describe the features that make a specific cell, tissue, or species susceptible to the mycotoxin. Important considerations include: (i) different mechanisms for bioactivation of AFB1 to its ultimate carcinogenic epoxide metabolite; (ii) the balance between bioactivation to and detoxification of the epoxide; (iii) the interaction of AFB1 epoxide with DNA and the mutational events leading to neoplastic transformation; (iv) the role of cytotoxicity in AFB1 carcinogenesis; (v) the significance of nonepoxide metabolites in toxicity; and (vi) the contribution of mycotoxin-unrelated disease processes. Although considerable controversy remains about the importance of specific events, a great deal has been learned about biochemical and molecular actions of AFB1.
Massey
T E
TE
Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada.
Stewart
R K
RK
Daniels
J M
JM
Liu
L
L
D016604:Aflatoxin B1 / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D004851:Epoxide Hydrolases / Q000502:physiology; D004852:Epoxy Compounds / Q000378:metabolism; D016158:Genes, p53 / Q000187:drug effects; D005982:Glutathione Transferase / Q000502:physiology; D006801:Humans; D008168:Lung / Q000378:metabolism; D009369:Neoplasms / Q000139:chemically induced*; D011519:Proto-Oncogenes / Q000187:drug effects
D004852:Epoxy Compounds; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases