title: Metabolic activation of benzo[g]chrysene in the human mammary carcinoma cell line MCF-7.
abstract: 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.
authors.affiliation: ABL-Basic Research Program, National Cancer Institute-Frederick Cancer Research & Development Center, Maryland 21702, USA.
authors.forename: R
authors.initials: R
authors.lastname: Agarwal
authors.forename: S L
authors.initials: SL
authors.lastname: Coffing
authors.forename: W M
authors.initials: WM
authors.lastname: Baird
authors.forename: A S
authors.initials: AS
authors.lastname: Kiselyov
authors.forename: R G
authors.initials: RG
authors.lastname: Harvey
authors.forename: A
authors.initials: A
authors.lastname: Dipple
mesh_terms: 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
chemical_list: D002273:Carcinogens; D002911:Chrysenes; D018736:DNA Adducts; C100422:benzo(g)chrysene