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© 1990 Oxford University Press

research-article

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

J. K. Wiencke 1 2, M. L. Dowell 1 and W. J. Bodell 3

1Department of Epidemiology and Biostatistics, School of Medicine, University of California San Francisco, CA 94143-0560, USA
2Laboratory of Radiobiology and Environmental Health, School of Medicine, University of California San Francisco, CA 94143-0560, USA
3Brain Tumor Research Center of the Department of Neurological Surgeiy, School of Medicine, University of California San Francisco, CA 94143-0560, USA

We examined the relationship between[a]benzo—DNA adducts and sister chromatid exchanges (SCEs) in human lymphocytes. Cultures of isolated phytohemagglutinin (PHA)-stimulated lymphocytes from two nonnal donors were treated with 0.01–5.0 µM 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 polyethylenimlne plates with the adduct produced by (+)-7ß,8{alpha}-dihydroxy-9{alpha},10{alpha}-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene. B[a]P-DNA adduct levels ranged from 0.02 to 8 adduds/107 nucleotides. SCE frequencies measuredin parallel cultures ranged from 8 to 46 SCEs/cell. At the same B[a] 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 andthe number of SCEs induced; slopes of the linear regressions of induced SCEs on B 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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