GSTM1 and APE1 Genotypes Affect Arsenic-Induced Oxidative Stress: A Repeated Measures Study

Details

• Personal Author:
  Breton CV ; Catalano PJ ; Christiani, David C. ; Hoffman E ; Kile ML ; Mahiuddin G ; Quamruzzaman Q ; Rahman M
• Description:
  Background: Chronic arsenic exposure is associated with an increased risk of skin, bladder and lung cancers. Generation of oxidative stress may contribute to arsenic carcinogenesis. Methods: To investigate the association between arsenic exposure and oxidative stress, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) was evaluated in a cohort of 97 women recruited from an arsenic-endemic region of Bangladesh in 2003. Arsenic exposure was measured in urine, toenails, and drinking water. Drinking water and urine samples were collected on three consecutive days. Susceptibility to oxidative stress was evaluated by genotyping relevant polymorphisms in glutathione-s transferase mu (GSTM1), human 8-oxoguanine glycosylase (hOGG1) and apurinic/apyrimidinic endonuclease (APE1) genes using the Taqman method. Data were analyzed using random effects Tobit regression to account for repeated measures and 8-OHdG values below the detection limit. Results: A consistent negative effect for APE1 was observed across water, toenail and urinary arsenic models. APE1 148 glu/glu + asp/glu genotype was associated with a decrease in logged 8-OHdG of 0.40 (95%CI -0.73, -0.07) compared to APE1 148 asp/asp. An association between total urinary arsenic and 8-OHdG was observed among women with the GSTM1 null genotype but not in women with GSTM1 positive. Among women with GSTM1 null, a comparison of the second, third, and fourth quartiles of total urinary arsenic to the first quartile resulted in a 0.84 increase (95% CI 0.27, 1.42), a 0.98 increase (95% CI 033, 1.66) and a 0.85 increase (95% CI 0.27, 1.44) in logged 8-OHdG, respectively. No effects between 8-OHdG and toenail arsenic or drinking water arsenic were observed. Conclusion: These results suggest the APE1 variant genotype decreases repair of 8-OHdG and that arsenic exposure is associated with oxidative stress in women who lack a functional GSTM1 detoxification enzyme. [Description provided by NIOSH]
• Subjects:
  Arsenic Carcinogens Environmental Exposure Genetics Inorganic Chemicals Lung Lung Diseases Neoplasms Occupational Health Respiratory System Respiratory Tract Diseases Risk Assessment Risk Factors Safety Skin Skin Diseases Urine Women

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• Keywords:
  Arsenic Compounds Bladder Cancer Carcinogenesis Exposure Levels Genes Humans Lung Cancer Oxidative Stress Risk Factors Skin Cancer Urine Chemistry

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• ISSN:
  1476-069X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  California ; Massachusetts ; OSHA Region 1 ; OSHA Region 9
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  39
• Volume:
  6
• NIOSHTIC Number:
  nn:20054415
• Citation:
  Environ Health 2007 Dec; 6:39
• Contact Point Address:
  Carrie V Breton, Harvard School of Public Health, Dept of Environmental Health, 665 Huntington Avenue, Boston, MA 02115
• Email:
  breton@usc.edu
• CAS Registry Number:
  Arsenic (CAS RN 7440-38-2)
• Federal Fiscal Year:
  2008
• Performing Organization:
  Harvard School of Public Health
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Environmental Health: A Global Access Science Source
• End Date:
  20280630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:6b3832bda2cdace90a289033453efb48177dcd02ed3d42cee176a11ef8825270e9144d720f5359f2e5dd7dd7d615691700b42b0a524ce2ec65a6b7cf70f8ca0e
• Download URL:
  https://stacks.cdc.gov/view/cdc/216990/cdc_216990_DS1.pdf
• File Type:
  [PDF - 305.71 KB ]