Nuclear envelope-dependent binding of aflatoxin B1 to DNA.
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.
Yoshizawa
H
H
Department of Toxicology and Microbial Chemistry, Faculty of Pharmaceutical Sciences, Science University of Tokyo, Japan.
Uchimaru
R
R
Ito
T
T
Tashiro
F
F
Ueno
Y
Y
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
D000348:Aflatoxins; D014239:Trichloroepoxypropane; D011092:Polyethylene Glycols; D017830:Octoxynol; D004247:DNA; D016604:Aflatoxin B1; D005978:Glutathione