Genotoxic effects of five polycyclic aromatic hydrocarbons in human and rat mammary epithelial cells

Environ Mol Mutagen. 1990;15(2):78-82. doi: 10.1002/em.2850150204.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Breast / cytology*
  • Breast / drug effects
  • DNA Replication / drug effects
  • Epithelial Cells
  • Epithelium / drug effects
  • Female
  • Humans
  • Mammary Glands, Animal / cytology*
  • Mammary Glands, Animal / drug effects
  • Mutagens*
  • Polycyclic Compounds / pharmacology*
  • Rats
  • Sister Chromatid Exchange / drug effects
  • Structure-Activity Relationship

Substances

  • Mutagens
  • Polycyclic Compounds