Chlorophyllin differentially modulates CYP1 gene expression in normal human mammary epithelial cells (NHMECs) exposed to benzopyrenes.
John-K; Divi-RL; Keshava-C; Whipkey-DL; Poirier-MC; Weston-A; Nath-J
97th AACR Annual Meeting, April 1-5, 2006, Washington D.C. Philadelphia, PA: American Association for Cancer Research, 2006 Apr; 47:5217
Benzo(a)pyrene (B[a]P), a carcinogen, and benzo(e)pyrene (B[e]P), a co-carcinogen, are ubiquitous environmental pollutants. Here, we examined the induction, and modulation by chlorophyllin (5uM) of CYP1A1 and CYP1B1 in NHMEC strains (M98015 and M98025) exposed to either B[a]P or B[e]P (4uM). Four exposure regimens were used: T1 - B[a]P or B[e]P alone (24h); T2 - B[a]P or B[e]P together with chlorophyllin (co-treatment, 24h); T3 - chlorophyllin pretreatment (24h) followed by B[a]P or B[e]P alone (24h); and T4 - chlorophyllin pretreatment (24h) followed by chlorophyllin plus B[a]P or B[e]P co-treatment (24h). Real-time PCR (TaqMan) was used to examine differences in CYP1A1 and CYP1B1 expression. T1 - B[a]P induced CYP1A1 35-fold in cell strain M98015 and 10-fold in cell strain M98025. B[a]P induced CYP1B1 23-fold in cell strain M98015 and 5-fold in cell strain M98025. Levels of CYP1A1 and CYP1B1 expression were unchanged in the presence of B[e]P, with the exception of a 2-fold increase in CYP1A1 in cell strain M98015. T2 - Co-treatment with chlorophyllin reduced B[a]P induction of CYP1A1 and CYP1B1 expression by 30% and 42%, respectively in M98015, and 37% and 21% in M98025. In contrast, chlorophyllin increased B[e]P induction of CYP1A1 and CYP1B1 by 148% and 75% respectively in M98015, and by 219%, and 132%, respectively in M98025. T3 - Pretreatment with chlorophyllin did not alter B[a]P induction of either enzyme in M98015, but in M98025 CYP1A1 and CYP1B1 levels were reduced by 29% and 50%, respectively. With chlorophyllin pretreatment B[e]P-induced CYP1A1 and CYP1B1 expression levels were mitigated by 3% and 4%, respectively in strain M98015 and 19% and 54%, respectively in strain M98025. T4 - When NHMECs were co-treated with B[a]P and chlorophyllin after chlorophyllin pretreatment, induction of CYP1A1 and CYP1B1 expression fell by 40% and 47% in M98025 and by 0% and 35% in M98015. B[e]P induction of CYP1A1 and CYP1B1 was modestly enhanced by T4 treatment in M98015, as was CYP1A1 expression in M98025. Complementary studies are in progress to define DNA adduct levels. Data for CYP1A1 and CYP1B1 expression levels show clear differences between metabolic events occurring in NHMECs exposed to the carcinogenic B[a]P and the non-carcinogenic B[e]P.
Carcinogens; Carcinogenicity; Carcinogenesis; Environmental-pollution; Pollution; Pollutants; Exposure-levels; Exposure-assessment
Abstract; Conference/Symposia Proceedings
97th American Association for Cancer Research Annual Meeting, April 1-5, 2006, Washington D.C.