EFFECT OF THE ROUTE OF BENZO[A]PYRENE ADMINISTRATION ON SISTER-CHROMATID EXCHANGE AND DNA-BINDING IN BONE-MARROW OF MICE DIFFERING WITH RESPECT TO CYTOCHROME-P450 1A1 INDUCTION

The effects of the route of benzo[a]pyrene administration on sister ch romatid exchange (SCE) and B[a]P diol epoxide (B[a]PDE)-DNA adducts fo rmation in bone marrow cells of Ah responsive (C57BL/6; B6) and Ah non -responsive (DBA/2; D2) mice were determined. Animals were treated int raperitoneally (i.p.), intragastrically (i.g.) or topically with two 1 00 mg/kg doses of benzo[a]pyrene 24 h apart and killed 96 h after the first treatment. Significant increase in the frequencies of SCE and th e level of B[a]PDE-DNA adducts as measured by synchronous fluorescence spectrophotometry were detected in D2 mice as compared to B6 mice. Th e route of administration had little effect on SCE levels in bone marr ow cells in D2 mice. In B6 mice higher levels of SCE were observed fol lowing i.p. administration as compared to i.g. or topical administrati on. In both strains the highest level of B[a]PDE-DNA adducts was forme d after i.p. administration of B[a]P. We conclude that the i.p. route of B[a]P administration is the most effective in inducing SCE and B[a] P-DNA adducts formation. SCE induction does not correlate linearly wit h the amount of B[a]PDE-DNA adducts formed in these cells after admini stration of the above dose of B[a]P. (C) 1997 Elsevier Science Ireland Ltd.