CYP1A1 and CYP1B1 gene expression and DNA adduct formation in normal human mammary epithelial cells exposed to benzo[a]pyrene in the absence or presence of chlorophyllin.
John-K; Divi-RL; Keshava-C; Orozco-CC; Schockley-ME; Richardson-DL; Poirier-MC; Nath-J; Weston-A
Cancer Lett 2010 Jun; 292(2):254-260
Benzo[a]pyrene (BP) is a potent pro-carcinogen and ubiquitous environmental pollutant. Here, we examined the induction and modulation of CYP1A1 and CYP1B1 and 10-(deoxyguanosin-N-2-yl)-7,8,9-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPdG) adduct formation in DNA from 20 primary normal human mammary epithelial cell (NHMEC) strains exposed to BP (4 mu M) in the absence or presence of chlorophyllin (5 mu M) Real-time polymerase chain reaction (RT-PCR) analysis revealed strong induction of both CYP1A1 and CYP1B1 by BP, with high levels of inter-individual variability Variable BPdG formation was found in all strains by r7, t8-dihydroxy-t-9, 10 epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE)-DNA chemiluminescence assay (CIA). Chlorophyllin mitigated BP-induced CYP1A1 and CYP1B1 gene expression in all 20 strains when administered with BP. Chlorophyllin, administered prior to BP-exposure, mitigated CYP1A1 expression in 18/20 NHMEC strains (p < 0 005) and CYP1B1 expression in 17/20 NHMEC strains (p < 0.005) Maximum percent reductions of CYP1A1 and CYP1B1 gene expression and BPdG adduct formation were observed when cells were pre-dosed with chlorophyllin followed by administration of the carcinogen with chlorophyllin (p < 0 005 for CYP1A1 and CYP1B1 expression and p < 0.0005 for BPdG adducts) Therefore, chlorophyllin is likely to be a good chemoprotective agent for a large proportion of the human population.
Biological-effects; Biological-factors; Chemical-hypersensitivity; Estrogenic-hormones; Genes; Genetic-factors; Glands; Glandular-disorders; Hormones; Humans; Mammary-glands;
Author Keywords: Real-time-PCR; BPDE-DNA chemiluminescence immunoassay; Chemoprevention; Chlorophyllin; Polycyclic aromatic hydrocarbons; DNA adducts
A Weston, CDC, NIOSH, MS-H2900,1095 Willowdale Rd, Morgantown, WV 26505