Molecular dosimetry of DNA adducts and sister chromatid exchanges in human lymphocytes treated with benzo[a]pyrene.
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 0.01-5.0 microM 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 greater than 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- tetrahydro-benzo[a]pyrene. B[a]P-DNA adduct levels ranged from 0.02 to 8 adducts/10(7) 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 regressions 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.
Wiencke
J K
JK
Department of Epidemiology and Biostatistics, School of Medicine, University of California, San Francisco 94143-0560.
McDowell
M L
ML
Bodell
W J
WJ
D001345:Autoradiography; D001564:Benzo(a)pyrene / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D004247:DNA / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010761:Phosphorus Radioisotopes; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D010761:Phosphorus Radioisotopes; D001564:Benzo(a)pyrene; D004247:DNA