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. 2010

Kaarthik John, and Rao L Divi, and Channa Keshava, and Christine C Orozco, and Marie E Schockley, and Diana L Richardson, and Miriam C Poirier, and Joginder Nath, and Ainsley Weston
Genetics and Developmental Biology Program, West Virginia University, Morgantown, WV, United States.

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 (4muM) in the absence or presence of chlorophyllin (5muM). 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.

UI MeSH Term Description Entries
D002735 Chlorophyllides Products of the hydrolysis of chlorophylls in which the phytic acid side chain has been removed and the carboxylic acids saponified. Chlorophyllide
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001189 Aryl Hydrocarbon Hydroxylases A large group of cytochrome P-450 (heme-thiolate) monooxygenases that complex with NAD(P)H-FLAVIN OXIDOREDUCTASE in numerous mixed-function oxidations of aromatic compounds. They catalyze hydroxylation of a broad spectrum of substrates and are important in the metabolism of steroids, drugs, and toxins such as PHENOBARBITAL, carcinogens, and insecticides. Microsomal Monooxygenases,Xenobiotic Monooxygenases,Hydroxylases, Aryl Hydrocarbon,Monooxygenases, Microsomal,Monooxygenases, Xenobiotic
D001564 Benzo(a)pyrene A potent mutagen and carcinogen. It is a public health concern because of its possible effects on industrial workers, as an environmental pollutant, an as a component of tobacco smoke. 3,4-Benzopyrene,3,4-Benzpyrene,3,4 Benzopyrene,3,4 Benzpyrene
D042361 Mammary Glands, Human Glandular tissue in the BREAST of human that is under the influence of hormones such as ESTROGENS; PROGESTINS; and PROLACTIN. In WOMEN, after PARTURITION, the mammary glands secrete milk (MILK, HUMAN) for the nourishment of the young. Human Mammary Gland,Human Mammary Glands,Mammary Alveoli, Human,Mammary Ducts, Human,Mammary Epithelia, Human,Mammary Epithelium, Human,Mammary Gland,Mammary Glands,Mammary Lobules, Human,Alveoli, Human Mammary,Alveolus, Human Mammary,Duct, Human Mammary,Ducts, Human Mammary,Epithelia, Human Mammary,Epithelium, Human Mammary,Gland, Human Mammary,Gland, Mammary,Glands, Human Mammary,Glands, Mammary,Human Mammary Alveoli,Human Mammary Alveolus,Human Mammary Duct,Human Mammary Ducts,Human Mammary Epithelia,Human Mammary Epithelium,Human Mammary Lobule,Human Mammary Lobules,Mammary Alveolus, Human,Mammary Duct, Human,Mammary Gland, Human,Mammary Lobule, Human
D018736 DNA Adducts The products of chemical reactions that result in the addition of extraneous chemical groups to DNA. DNA Adduct,Adduct, DNA,Adducts, DNA
D019363 Cytochrome P-450 CYP1A1 A liver microsomal cytochrome P-450 monooxygenase capable of biotransforming xenobiotics such as polycyclic hydrocarbons and halogenated aromatic hydrocarbons into carcinogenic or mutagenic compounds. They have been found in mammals and fish. This enzyme, encoded by CYP1A1 gene, can be measured by using ethoxyresorufin as a substrate for the ethoxyresorufin O-deethylase activity. CYP1A1,EROD,Ethoxyresorufin O-Deethylase,7-Ethoxyresorufin O-Deethylase,CYP 1A1,CYP1A1 Protein,Cytochrome P450 IA1,Ethoxyresorufin Dealkylase,Ethylresorufin O-Deethylase,Cytochrome P 450 CYP1A1
D020133 Reverse Transcriptase Polymerase Chain Reaction A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols. Polymerase Chain Reaction, Reverse Transcriptase,Reverse Transcriptase PCR,PCR, Reverse Transcriptase,Transcriptase PCR, Reverse
D065633 Cytochrome P-450 CYP1B1 A cytochrome P450 aryl hydrocarbon hydroxylase that has specificity for ESTROGENS which it converts into 4-hydroxy estrogens. CYP1B1 has been shown to be physiologically important for FETAL DEVELOPMENT with mutations in the CYP1B1 gene resulting in congenital forms of GLAUCOMA and Peter's anomaly. Cytochrome P450 CYP1B1,Cytochrome P450, Family 1, Subfamily B, Polypeptide 1,Cytochrome P4501B1,Cytochrome P 450 CYP1B1,P450 CYP1B1, Cytochrome

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