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 studies have demonstrated that anti- BgC-11,12-dihydrodiol 13,14-epoxide (anti-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 32P-postlabeling, and specific adducts were identified through comparisons with adducts obtained by the reaction of the racemic syn- and anti-BgCDEs with calf thymus DNA and with purine deoxyribonucleoside-3'-phosphates in vitro. It was found 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-epoxide metabolites. BgC is therefore a potential environmental risk to humans. The major BgC-DNA adducts formed from both the dihydrodiol-epoxide diastereomers were deoxyadenosine adducts. Thus, BgC has DNA-binding properties that are very similar to those of the potent mammary carcinogens 7,12-dimethylbenz[a]anthracene and dibenzo[a,l]pyrene.
Agarwal
R
R
ABL-Basic Research Program, National Cancer Institute-Frederick Cancer Research & Development Center, Maryland 21702, USA.
Coffing
S L
SL
Baird
W M
WM
Kiselyov
A S
AS
Harvey
R G
RG
Dipple
A
A
D001711:Biotransformation; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002273:Carcinogens / Q000493:pharmacokinetics*; D002911:Chrysenes / Q000493:pharmacokinetics*; D018736:DNA Adducts / Q000378:metabolism; D005260:Female; D006801:Humans; D014407:Tumor Cells, Cultured
D002273:Carcinogens; D002911:Chrysenes; D018736:DNA Adducts; C100422:benzo(g)chrysene