Oxidative DNA damage and global DNA hypomethylation are related to folate deficiency in chromate manufacturing workers.

Exposure to hexavalent chromium [Cr (VI)] can cause DNA damage, genetic instability and increase the risk of cancer development. Folate deficiency affects DNA methylation and reduces the stability of the genetic material. However, the correlation between folate deficiency and DNA damage has never been clearly elucidated in chromate workers. In this study, we recruited one hundred and fifteen workers from chromate producing facilities as testing subjects and sixty local residents without chromium exposure history served as controls. The results showed an evident accumulation of Cr in peripheral red blood cells accompanied by a significantly decreased serum folate in chromate exposed workers. The decreased serum folate was associated with an increased urinary 8-hydroxy-2'-deoxyguanosine, DNA strand breaks and global DNA hypomethylation. These findings suggest that chronic occupational chromate exposure could induce folate depletion, which may further promote DNA damages and global DNA hypomethylation. Adequate folate supplement may provide benefit to chromate sufferers in stabilization of genetic material and reduce the risk of cancer development.

[1]  Kent D. Sugden,et al.  The role of chromium(V) in the mechanism of chromate-induced oxidative DNA damage and cancer. , 2000, Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer.

[2]  S. Wise,et al.  Hexavalent Chromium-Induced DNA Damage and Repair Mechanisms , 2008, Reviews on environmental health.

[3]  Sang-Woon Choi,et al.  Folate status: effects on pathways of colorectal carcinogenesis. , 2002, The Journal of nutrition.

[4]  A. Tangoku,et al.  Aberrant DNA methylation of some tumor suppressor genes in lung cancers from workers with chromate exposure , 2011, Molecular carcinogenesis.

[5]  P. Brandt-Rauf,et al.  CYP2E1 mRNA expression, genetic polymorphisms in peripheral blood lymphocytes and liver abnormalities in Chinese VCM-exposed workers. , 2008, International journal of occupational medicine and environmental health.

[6]  G. Jia,et al.  Renal impairment caused by chronic occupational chromate exposure , 2011, International archives of occupational and environmental health.

[7]  Z. Chai,et al.  Increased oxidative DNA damage, as assessed by urinary 8-hydroxy-2'-deoxyguanosine concentrations, and serum redox status in persons exposed to mercury. , 2005, Clinical chemistry.

[8]  Li-hong Xu,et al.  Oral administration of Cr(VI) induced oxidative stress, DNA damage and apoptotic cell death in mice. , 2006, Toxicology.

[9]  A. Ochiai,et al.  Microsatellite instability and protein expression of the DNA mismatch repair gene, hMLH1, of lung cancer in chromate‐exposed workers , 2005, Molecular carcinogenesis.

[10]  R. Melnick,et al.  Hexavalent Chromium Is Carcinogenic to F344/N Rats and B6C3F1 Mice after Chronic Oral Exposure , 2008, Environmental health perspectives.

[11]  J. Lai,et al.  Effect of genotoxic exposure to chromium among electroplating workers in Taiwan. , 2001, The Science of the total environment.

[12]  R. Jacob.  Folate, DNA methylation, and gene expression: factors of nature and nurture. , 2000, The American journal of clinical nutrition.

[13]  Yi-Fang Chou,et al.  Mitochondrial DNA deletions of blood lymphocytes as genetic markers of low folate-related mitochondrial genotoxicity in peripheral tissues , 2009, European journal of nutrition.

[14]  C. Klein,et al.  Chromate-induced epimutations in mammalian cells. , 2002, Environmental health perspectives.

[15]  N. Sapojnikova,et al.  Chromium (VI) Can Activate and Impair Antioxidant Defense System , 2011, Biological Trace Element Research.

[16]  Kazuya Kondo,et al.  The reduced expression and aberrant methylation of p16(INK4a) in chromate workers with lung cancer. , 2005, Lung cancer.

[17]  Steven R Patierno,et al.  Chromium genotoxicity: A double-edged sword. , 2010, Chemico-biological interactions.

[18]  V. Balachandar,et al.  Evaluation of the genetic alterations in direct and indirect exposures of hexavalent chromium [Cr(VI)] in leather tanning industry workers North Arcot District, South India , 2010, International archives of occupational and environmental health.

[19]  T. Liu,et al.  Folate deficiency-induced oxidative stress and apoptosis are mediated via homocysteine-dependent overproduction of hydrogen peroxide and enhanced activation of NF-kappaB in human Hep G2 cells. , 2001, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[20]  H. Kuo,et al.  Chromium (VI) induced oxidative damage to DNA: increase of urinary 8-hydroxydeoxyguanosine concentrations (8-OHdG) among electroplating workers , 2003, Occupational and environmental medicine.

[21]  S. Duthie.  Folate and cancer: how DNA damage, repair and methylation impact on colon carcinogenesis , 2011, Journal of Inherited Metabolic Disease.

[22]  Max Costa,et al.  Toxicity and Carcinogenicity of Chromium Compounds in Humans , 2006 .

[23]  D. Bagchi,et al.  Cytotoxicity and oxidative mechanisms of different forms of chromium. , 2002, Toxicology.

[24]  A. Georgakilas,et al.  Oxidative stress, DNA methylation and carcinogenesis. , 2008, Cancer letters.

[25]  P. Tchounwou,et al.  Oxidative stress, DNA damage, and antioxidant enzyme activity induced by hexavalent chromium in Sprague‐Dawley rats , 2009, Environmental toxicology.

[26]  A. Zhitkovich,et al.  Elevated levels of DNA-protein crosslinks and micronuclei in peripheral lymphocytes of tannery workers exposed to trivalent chromium. , 2003, Mutagenesis.

[27]  N. Koksal,et al.  The role of oxidative stress in bronchoconstriction due to occupational sulfur dioxide exposure. , 2003, Clinica chimica acta; international journal of clinical chemistry.

[28]  M. Fenech.  The role of folic acid and Vitamin B12 in genomic stability of human cells. , 2001, Mutation research.

[29]  Max Costa,et al.  Epigenetics in metal carcinogenesis: nickel, arsenic, chromium and cadmium. , 2009, Metallomics : integrated biometal science.

[30]  G. Abbritti,et al.  Primary DNA damage in chrome-plating workers. , 2003, Toxicology.

[31]  A. Zhitkovich,et al.  Genetic and epigenetic mechanisms in metal carcinogenesis and cocarcinogenesis: nickel, arsenic, and chromium. , 2008, Chemical research in toxicology.

[32]  K. Salnikow,et al.  The role of oxidative stress in nickel and chromate genotoxicity. , 2002 .

[33]  S. Patierno,et al.  Lung Inflammation, Injury, and Proliferative Response after Repetitive Particulate Hexavalent Chromium Exposure , 2009, Environmental health perspectives.

[34]  M. Yousef,et al.  Biochemical Study on the Protective Role of Folic Acid in Rabbits Treated with Chromium (VI) , 2006, Journal of environmental science and health. Part. B, Pesticides, food contaminants, and agricultural wastes.

[35]  H. McNulty,et al.  Global DNA and p53 region-specific hypomethylation in human colonic cells is induced by folate depletion and reversed by folate supplementation. , 2006, The Journal of nutrition.

[36]  T. Mukherjee,et al.  Free radical scavenging behavior of folic acid: evidence for possible antioxidant activity. , 2001, Free radical biology & medicine.

[37]  S. Duthie,et al.  Increased uracil misincorporation in lymphocytes from folate-deficient rats , 2000, British Journal of Cancer.

[38]  S. Vollset,et al.  Long- and short-term effects of tobacco smoking on circulating concentrations of B vitamins. , 2010, Clinical Chemistry.

[39]  Y. Komatsu,et al.  Four week supplementation with mixed fruit and vegetable juice concentrates increased protective serum antioxidants and folate and decreased plasma homocysteine in Japanese subjects. , 2007, Asia Pacific journal of clinical nutrition.

[40]  G. Rampersaud,et al.  Genomic DNA methylation decreases in response to moderate folate depletion in elderly women. , 2000, The American journal of clinical nutrition.

[41]  C. Matté,et al.  Chronic hyperhomocysteinemia alters antioxidant defenses and increases DNA damage in brain and blood of rats: Protective effect of folic acid , 2009, Neurochemistry International.

[42]  A. Bird,et al.  Oxidative damage to methyl-CpG sequences inhibits the binding of the methyl-CpG binding domain (MBD) of methyl-CpG binding protein 2 (MeCP2). , 2004, Nucleic acids research.

[43]  S. Mattagajasingh,et al.  Carcinogenic chromium(VI)‐induced protein oxidation and lipid peroxidation: implications in DNA–protein crosslinking , 2008, Journal of applied toxicology : JAT.

[44]  Hong Sun,et al.  Effects of nickel, chromate, and arsenite on histone 3 lysine methylation. , 2009, Toxicology and applied pharmacology.

[45]  S. Duthie,et al.  Impact of folate deficiency on DNA stability. , 2002, The Journal of nutrition.

[46]  Hong Sun,et al.  Modulation of histone methylation and MLH1 gene silencing by hexavalent chromium. , 2009, Toxicology and applied pharmacology.