Molecular dosimetry of DNA adducts and sister chromatid exchanges in human lymphocytes treatedthricts and sister chroiinatid exchanges un human lymphocytes treated with benzo[a]pyrene

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Abstract
We examined the relationship between benzo[a]pyrene-DNA adducts and sister chromatid exchanges (SCEs) in human lymphocytes. Cultures of isolated phytohemagglutinin (PHA)-stimulated lymphocytes from two normal donors were treated with O.01-5.0 .mu.M B[a]P from 24 to 72 h of culture. Using the highly sensitive 32P-postlabeling assay, we identified seven B[a]P-DNA adducts, one of which accounted for >90% of the total DNA modifications. This adduct comigrated on polyethylenimine plates with the adduct produced by(+)-7.beta.,8.alpha.-dihydroxy-9.alpha.,10.alpha.-epoxy-7,8,9,10-tetrahydrozbenzo[.alpha.]pyrene, B[a]P-DNA adduct levels ranged from 0.02 to 8 adducts/107 nucleotides. SCE frequencies measured in parallel cultures ranged from 8 to 46 SCEs/cell. At the same B[a]P concentrations, B[a]P-induced SCE frequencies and B[a]P-DNA adduct levels were higher in lymphocytes from donor 1 than in lymphocytes from donor 2. There was a linear correlation between the number of B[a]P-DNA adducts and the number of SCEs induced; slopes of the linear regression of induced SCEs on B[a]P-DNA adducts were similar for both donors. Our data suggest that SCE induction by B[a]P in human lymphocytes results from covalent DNA modification.

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