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.