METABOLIC-ACTIVATION OF BENZO[G]CHRYSENE IN THE HUMAN MAMMARY-CARCINOMA CELL-LINE MCF-7

Benzo[g]chrysene (BgC) is an environmental pollutant, and recent studi es have demonstrated that anti-BgC-11,12-dihydrodiol 13,14-epoxide (an ti-BgCDE) is a potent mammary carcinogen in rats. To determine whether BgC can be metabolically activated to anti-BgCDE in human cells, the human mammary carcinoma cell line MCF-7 was treated with BgC and with the racemic trans-3,4- and 11,12 dihydrodiols. The DNA adducts formed in these experiments were examined using P-32-postlabeling, and specif ic adducts were identified through comparisons with adducts obtained b y the reaction of the racemic syn- and anti-BgCDEs with calf thymus DN A and with purine deoxyribonucleoside-3'-phosphates in vitro. It was f ound that BgC is metabolically activated in MCF-7 cells to form major DNA adducts through both the syn- and anti-11,12-dihydrodiol 13,14-epo xide metabolites. BgC is therefore a potential environmental risk to h umans. The major BgC-DNA adducts formed from both the dihydrodiol-epox ide diastereomers were deoxyadenosine adducts. Thus, BgC has DNA-bindi ng properties that are very similar to those of the potent mammary car cinogens 7,12-dimethylbenz[a]anthracene and dibenzo[a,l]pyrene.