title: Genotoxic effects of five polycyclic aromatic hydrocarbons in human and rat mammary epithelial cells.
abstract: Five polycyclic aromatic hydrocarbons (PAHs) of different carcinogenic activities were evaluated for their effects on DNA synthesis (3HTdR labeling index (L.I.] of rat and human mammary epithelial cells (MEC) and for their effects on chromosomes in MEC-mediated sister chromatid exchange (SCE) assays. When compared with DMSO-treated cells, exposures of rat MEC to the two most potent carcinogens (5 micrograms/ml for 24 hr), i.e., 7,12-dimethylbenz(a)anthracene (DMBA) and benzo(a)pyrene (B[a]P), resulted in a 45-62% reduction in the L.I. of rat MEC. Another carcinogen, 20-methylcholanthrene (MCA), produced a 35-48% reduction in L.I., while the noncarcinogenic PAHs, 1,2-benzanthracene (BA) and benzo(e)pyrene (B[e]P), showed no effect. Similarly, exposures of human MEC to DMBA and B[a]P resulted in a 50-90% depression in L.I. while BA was significantly less effective (30% reduction). When co-cultivated with Chinese hamster V-79 cells in the presence of PAH, both rat and human MEC can activate and release the active metabolites to induce SCE in V-79 cells. In the rat MEC-mediated assay for all 5 PAHs, the frequencies of SCE per chromosome in DMBA-, B[a]P-, MCA-, BA-, B[e]P-, and DMSO (solvent control)-treated groups were 6, 3, 1.4, 0.7, 0.4, and 0.3, respectively. DMBA was most effective in increasing SCE, while B[e]P was ineffective. In the human MEC-mediated assay, B[a]P was more effective than DMBA in inducing SCE, and the frequencies of SCE per chromosome were 4.5 and 3.6 in B[a]P- and DMBA-treated groups, respectively. Comparing depression of L.I., SCE, and in vivo carcinogenicity for the 5 PAHs, SCE mediated by rat MEC is better correlated with carcinogenicity in rat than L.I. depression.
authors.affiliation: Department of Pathology, University of Maryland School of Medicine, Baltimore 21201.
authors.forename: S S
authors.initials: SS
authors.lastname: Mane
authors.forename: D M
authors.initials: DM
authors.lastname: Purnell
authors.forename: I C
authors.initials: IC
authors.lastname: Hsu
mesh_terms: D000818:Animals; D001940:Breast / Q000166:cytology* / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D005260:Female; D006801:Humans; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000187:drug effects; D009153:Mutagens; D011083:Polycyclic Compounds / Q000494:pharmacology*; D051381:Rats; D012854:Sister Chromatid Exchange / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D009153:Mutagens; D011083:Polycyclic Compounds