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

Details

• Personal Author:
  Divi RL ; John K ; Keshava C ; Nath J ; Orozco CC ; Poirier MC ; Richardson DL ; Schockley ME ; Weston A
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Biological Factors Endocrine System Estrogens Genetics Hydrocarbons Hypersensitivity Occupational Health Polycyclic Aromatic Hydrocarbons Safety
• Keywords:
  Author Keywords: Real-time-PCR Biological-effects Biological-factors BPDE-DNA Chemiluminescence Immunoassay Chemical-hypersensitivity Chemoprevention Chlorophyllin DNA Adducts Estrogenic-hormones Genes Genetic-factors Glands Glandular-disorders Hormones Humans Mammary-glands Polycyclic Aromatic Hydrocarbons

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• ISSN:
  0304-3835
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Maryland ; OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  254-260
• Volume:
  292
• Issue:
  2
• NIOSHTIC Number:
  nn:20037039
• Citation:
  Cancer Lett 2010 Jun; 292(2):254-260
• Contact Point Address:
  A Weston, CDC, NIOSH, MS-H2900,1095 Willowdale Rd, Morgantown, WV 26505
• Federal Fiscal Year:
  2010
• Peer Reviewed:
  True
• Source Full Name:
  Cancer Letters
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:06b0e6443146726e82309c5d3241f8528a18b953446a68308a53068204ef911a270838acc12f5b65027bc36551a93e18f6ed325b9030eec4ba151e559a3fced4
• Download URL:
  https://stacks.cdc.gov/view/cdc/188211/cdc_188211_DS1.pdf
• File Type:
  [PDF - 332.45 KB ]