Diesel particulate extract (DPE), a mixture containing polycyclic aromatic hydrocarbons, is a major environmental pollutant. Previously, we showed the existence of inter-individual variations in induction of CYP1A1 and CYP1B1 by the polycyclic aromatic hydrocarbon benzo[a]pyrene. Here we have investigated the ability of DPE to induce a variety of genes, including CYP1A1 and CYP1B1, in normal human mammary epithelial cells. Further, we investigated the ability of chrorophyllin to mitigate the effects of DPE. normal human mammary epithelial cells were subjected to four separate 24h DPE (200 microgram g/ml, organic extract) treatments: DPE alone, DPE plus chrorophyllin (5 microgram M), chrorophyllin pretreatment (24h) followed by DPE, and chrorophyllin pretreatment followed by DPE plus chrorophyllin. Following exposure, gene expression was monitored by DNA oligonucleotide microarrays (U133A, Affymetrix). Of the total 22,000 genes present on the array, exposure to DPE alone altered expression of 235 genes by at least 2 fold (111 genes induced and 124 genes reduced). In particular, CYP1A1 and CYP1B1 were induced by 10-fold and 6-fold, respectively (r = 0.89, p<0.02). Limited induction of both CYP1A1 and CYP1B1 was observed in the presence of all three chrorophyllin treatment regimens. Maximal mitigation of the effects of DPE was observed in the treatment group where cells were pretreated chlorophyllin followed by DPE plus chlorophyllin. (CYP1A1 52%, p<0.02; CYP1B1 38%, p<0.03). Also chrorophyllin mitigated the induction of several other DPE-induced genes (PTGS2, ENPP2, NCOA1, PLA2G4A, S100A8 and S100A9). Thus, chrorophyllin may be beneficial when used as a dietary supplement for individuals exposed to environmental and occupational chemical carcinogens.
CDC, Toxicol & Mol Biol Lab, NIOSH, Morgantown, WV 26505