6533b85bfe1ef96bd12bb6d0

RESEARCH PRODUCT

DNA adduct levels associated with p53 induction and delay of MCF-7 cells in S phase after exposure to benzo[g]chrysene dihydrodiol epoxide enantiomers.

subject

description

Optically active isomers of a mammary carcinogen, anti-benzo[g]chrysene 11, 12-dihydrodiol 13, 14-epoxide, react to different extents with DNA and generate DNA adducts that differ in their stereochemistry. In the study reported here, the effect of these two enantiomers on the progress of human breast carcinoma MCF-7 cells through the cell cycle was investigated. Each enantiomer caused the cells to accumulate in the S phase, but a higher dose of the benzo[g]chrysene 11S, 12R-dihydrodiol 13R, 14S-epoxide than of its enantiomer was required to induce this effect. Similarly, induction of p53 also required a higher dose of benzo[g]chrysene 11S, 12R-dihydrodiol 13R, 14S-epoxide. Postlabeling studies indicated that the latter enantiomer also caused less modification of MCF-7 cell DNA for a given level of exposure than did benzo[g]chrysene 11R, 12S-dihydrodiol 13S, 14R-epoxide. These results suggest that p53 induction and delay in the S phase are similarly related to DNA binding and that a level of binding of the order of 1 adduct per 10(5) nucleotides is associated with these effects.