title: Nuclear envelope-dependent binding of aflatoxin B1 to DNA.
abstract: The function of nuclear envelope in the activation of aflatoxin B1 (AFB1) was investigated. Pretreatment of rats by phenobarbital or polychlorobiphenyl induced markedly the nuclei-dependent binding of AFB1 to DNA as well as the drug-metabolizing enzymes, such as aminopyrine-N-demethylase and epoxide hydratase. The high sensitivity of AFB1 activation to SKF-525A, a low inducibility of 3-methylcholanthrene for AFB1 activation and the removal of nuclear AFB1 activation by Triton X-100 indicate that the AFB1 binding to DNA is mediated by P-450 system localized in the nuclear envelope. In the intact nuclei, trichloropropane oxide, a potent inhibitor of epoxide hydratase, caused no significant increment in AFB1 binding to DNA. While in the reconstructed system composed of microsomes and stripped nuclei prepared by Triton X-100 treatment, this inhibitor caused a marked elevation of AFB1 binding. This evidence supports an assumption that AFB1-2,3-oxide produced by the microsomal oxygenase may be hydrolyzed by the microsomal epoxide hydratase, whereas the nuclear envelope-mediated AFB1-2,3-oxide is insensitive to the nuclear epoxide hydratase.
authors.affiliation: Department of Toxicology and Microbial Chemistry, Faculty of Pharmaceutical Sciences, Science University of Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yoshizawa
authors.forename: R
authors.initials: R
authors.lastname: Uchimaru
authors.forename: T
authors.initials: T
authors.lastname: Ito
authors.forename: F
authors.initials: F
authors.lastname: Tashiro
authors.forename: Y
authors.initials: Y
authors.lastname: Ueno
mesh_terms: D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D004247:DNA / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009685:Nuclear Envelope / Q000378:metabolism*; D017830:Octoxynol; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014239:Trichloroepoxypropane / Q000494:pharmacology
chemical_list: D000348:Aflatoxins; D014239:Trichloroepoxypropane; D011092:Polyethylene Glycols; D017830:Octoxynol; D004247:DNA; D016604:Aflatoxin B1; D005978:Glutathione