Biological Trace Element Research

, Volume 170, Issue 1, pp 84–93 | Cite as

Natural Antioxidants Against Arsenic-Induced Genotoxicity

  • Munesh Kumar
  • Minakshi Lalit
  • Rajesh ThakurEmail author


Arsenic is present in water, soil, and air in organic as well as in inorganic forms. However, inorganic arsenic is more toxic than organic and can cause many diseases including cancers in humans. Its genotoxic effect is considered as one of its carcinogenic actions. Arsenic can cause DNA strand breaks, deletion mutations, micronuclei formation, DNA-protein cross-linking, sister chromatid exchange, and DNA repair inhibition. Evidences indicate that arsenic causes DNA damage by generation of reactive free radicals. Nutritional supplementation of antioxidants has been proven highly beneficial against arsenic genotoxicity in experimental animals. Recent studies suggest that antioxidants protect mainly by reducing excess free radicals via restoring the activities of cellular enzymatic as well as non-enzymatic antioxidants and decreasing the oxidation processes such as lipid peroxidation and protein oxidation. The purpose of this review is to summarize the recent literature on arsenic-induced genotoxicity and its mitigation by naturally derived antioxidants in various biological systems.


Genotoxicity Antioxidants Oxidative stress Free radicals Inorganic arsenic 



National Research Council


Reactive oxygen species


Superoxide dismutase






δ-Aminolevulinic acid dehydratase


Meso-2,3-dimercaptosuccinic acid


δ-Aminolevulinic acid


Glutathione peroxidase


S-Adenosyl methionine




Xanthine oxidase


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no competing interests.

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed Consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Waalkes MP, Fox DA, States JC, Patierno SR, McCabe MJ Jr (2000) Metals and disorders of cell accumulation: modulation of apoptosis and cell proliferation. Toxicol Sci 56:255–261PubMedCrossRefGoogle Scholar
  2. 2.
    Knowles FC, Benson AA (1984) The enzyme inhibitory form of inorganic arsenic. Z Gesamten Hyg 30:625–626Google Scholar
  3. 3.
    Bettley FR, O’Shea JA (1975) The absorption of arsenic and its relation to carcinoma. Br J Dermatol 92:563–568PubMedCrossRefGoogle Scholar
  4. 4.
    Landolph JR (1994) Molecular mechanisms of transformation of C3H/10T1/2 C1 8 mouse embryo cells and diploid human fibroblasts by carcinogenic metal compounds. Environ Health Perspect 102:119–125PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Chen CJ, Wang CJ (1990) Ecological correlation between arsenic level in well water and age-adjusted mortality from malignant neoplasms. Cancer Res 50:5470–5474PubMedGoogle Scholar
  6. 6.
    Matschullat J (2000) Arsenic in the geosphere—a review. Sci Total Environ 249:297–312PubMedCrossRefGoogle Scholar
  7. 7.
    NRC (1999) Arsenic in the drinking water. National Research Council, National Academy Press, Washington, D.CGoogle Scholar
  8. 8.
    Smedley PL, Kinniburgh DG (2002) A review of the source, behaviour and distribution of arsenic in natural waters. Appl Geochem 17:517–568CrossRefGoogle Scholar
  9. 9.
    Mitra AK, Bose BK, Kabir H, Das BK, Hussain M (2002) Arsenic-related health problems among hospital patients in southern Bangladesh. J Health Popul Nutr 20:198–204PubMedGoogle Scholar
  10. 10.
    Pandey PK, Yadav S, Nair S, Bhui A (2002) Arsenic contamination of the environment: a new perspective from central-east India. Environ Int 28:235–245PubMedCrossRefGoogle Scholar
  11. 11.
    Chowdhury UK, Biswas BK, Chowdhury TR et al (2000) Ground water arsenic contamination in Bangladesh and West Bengal, India. Environ Health Perspect 108:393–397PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Nordstrom DK (2002) Worldwide occurrences of arsenic in ground water. Science 296:2143–2145PubMedCrossRefGoogle Scholar
  13. 13.
    United States Environmental Protection Agency (2001) National primary drinking water regulations; arsenic and clarifications to compliance and new source contaminants monitoring. Fed Regist 66:6976–7066Google Scholar
  14. 14.
    Hopenhayn-Rich C, Biggs ML, Smith AH, Kalman DA, Moore LE (1996) Methylation study of a population environmentally exposed to arsenic in drinking water. Environ Health Perspect 104:620–628PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Tam GK, Charbonneau SM, Bryce F, Pomroy C, Sandi E (1979) Metabolism of inorganic arsenic (74As) in humans following oral ingestion. Toxicol Appl Pharmacol 50:319–322PubMedCrossRefGoogle Scholar
  16. 16.
    Foa V, Colombi A, Maroni M, Buratti M, Calzaferri G (1984) The speciation of the chemical forms of arsenic in the biological monitoring of exposure to inorganic arsenic. Sci Total Environ 34:241–259PubMedCrossRefGoogle Scholar
  17. 17.
    Cullen WR, Reimer KJ (1989) Arsenic speciation in the environment. Chem Rev 89:713–764CrossRefGoogle Scholar
  18. 18.
    Mandal BK, Ogra Y, Suzuki KT (2001) Identification of dimethylarsinous and monomethylarsonous acids in human urine of the arsenic-affected areas in West Bengal, India. Chem Res Toxicol 14:371–378PubMedCrossRefGoogle Scholar
  19. 19.
    Vahter M, Concha G (2001) Role of metabolism in arsenic toxicity. Pharmacol Toxicol 89:1–5PubMedCrossRefGoogle Scholar
  20. 20.
    Shi H, Shi X, Liu KJ (2004) Oxidative mechanism of arsenic toxicity and carcinogenesis. Mol Cell Biochem 255:67–78PubMedCrossRefGoogle Scholar
  21. 21.
    Valko M, Morris H, Cronin MT (2005) Metals, toxicity and oxidative stress. Curr Med Chem 12:1161–1208PubMedCrossRefGoogle Scholar
  22. 22.
    Martinez VD, Vucic EA, Adonis M, Gil L, Lam WL (2011) Arsenic biotransformation as a cancer promoting factor by inducing DNA damage and disruption of repair mechanisms. Mol Biol Int 2011, 718974. doi: 10.4061/2011/718974 PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Gonsebatt ME, Vega L, Salazar AM, Montero R, Guzman P, Blas J et al (1997) Cytogenetic effects in human exposure to arsenic. Mutat Res 386(Suppl 3):219–228PubMedCrossRefGoogle Scholar
  24. 24.
    Biggs ML, Kalman DA, Moore LE, Hopenhayn-Rich C, Smith MT, Smith AH (1997) Relationship of urinary arsenic to intake estimates and a biomarker of effect, bladder cell micronuclei. Mutat Res 386:185–195PubMedCrossRefGoogle Scholar
  25. 25.
    Tinwell H, Stephens SC, Ashby J (1991) Arsenite as the probable active species in the human carcinogenicity of arsenic: mouse micronucleus assays on Na and K arsenite, orpiment, and Fowler’s solution. Environ Health Perspect 95:205–210PubMedCentralPubMedGoogle Scholar
  26. 26.
    Barrett JC, Lamb PW, Wang TC, Lee TC (1989) Mechanisms of arsenic-induced cell transformation. Biol Trace Elem Res 21:421–429PubMedCrossRefGoogle Scholar
  27. 27.
    IARC Working Group on the Evaluation of Carcinogenic Risks to Humans (2004) Some drinking-water disinfectants and contaminants, including arsenic. IARC Monogr Eval Carcinog Risks Hum 84:1–477Google Scholar
  28. 28.
    IARC (1980) Arsenic and arsenic compounds. Some metals and metallic compounds. IARC Monogr Eval Carcinog Risks Hum 23:39–141Google Scholar
  29. 29.
    IARC (1987) Arsenic. Overall evaluation of carcinogenicity: an updating of IARC monographs Volumes 1–42. International Agency for Research on Cancer, Lyon, pp 100–106, Suppl 7 Google Scholar
  30. 30.
    Leonard A, Lauwerys RR (1980) Carcinogenicity, teratogenicity, and mutagenicity of arsenic. Mutat Res 75:49–62PubMedCrossRefGoogle Scholar
  31. 31.
    Tsai SM, Wang TS, Ko YC (1999) Mortality for certain diseases in areas with high levels of arsenic in drinking water. Arch Environ Health 54(Suppl 3):186–193PubMedCrossRefGoogle Scholar
  32. 32.
    Smith AH, Arroyo AP, Mazumder DNG, Kosnett MJ, Hernandez AL, Beeris M et al (2000) Arsenic-induced skin lesions among Atacameno people in Northern Chile despite good nutrition and centuries of exposure. Environ Health Perspect 108(Suppl 7):617–620PubMedCentralPubMedGoogle Scholar
  33. 33.
    Col M, Col C, Soran A, Sayli BS, Ozturk S (1999) Arsenic related Bowen’s disease, palmar keratosis, and skin cancer. Environ Health Perspect 107(Suppl 8):687–689PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Ahmad S, Kitchin KT, Cullen WR (2000) Arsenic species that causes release of iron from ferritin and generation of activated oxygen. Arch Biochem Biophys 382:195–202PubMedCrossRefGoogle Scholar
  35. 35.
    Hei TK, Liu SX, Waldren C (1998) Mutagenicity of arsenic in mammalian cells: role of reactive oxygen species. Proc Natl Acad Sci U S A 95:8103–8107PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Li D, Morimoto K, Takeshita T, Lu Y (2001) Arsenic induces DNA damage via reactive oxygen species in human cells. Environ Health Prev Med 6:27–32PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Abernathy CO, Liu YP, Longfellow D, Aposhian HV, Beck B, Fowler B, Goyer R, Menzer R, Rossman T, Thompson C, Waalkes M (1999) Arsenic: health effects, mechanisms of actions, and research issues. Environ Health Perspect 107:593–597PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Lynn S, Gurr JR, Lai HT, Jan KY (2000) NADH oxidase activation is involved in arsenite-induced oxidative DNA damage in human vascular smooth muscle cells. Circ Res 86:514–519PubMedCrossRefGoogle Scholar
  39. 39.
    Wu MM, Chiou HY, Wang TW, Hsueh YM, Wang IH, Chen CJ, Lee TC (2001) Association of blood arsenic levels with increased reactive oxidants and decreased antioxidant capacity in a human population of northeastern Taiwan. Environ Health Perspect 1091:1011–1017CrossRefGoogle Scholar
  40. 40.
    Kitchin KT, Wallace K (2008) Evidence against the nuclear in situ binding of arsenicals—oxidative stress theory of arsenic carcinogenesis. Toxicol Appl Pharmacol 232:252–257PubMedCrossRefGoogle Scholar
  41. 41.
    Bau DT, Wang TS, Chung CH, Wang AS, Jan KY (2002) Oxidative DNA adducts and DNA-protein cross-links are the major DNA lesions induced by arsenite. Environ Health Perspect 110:753–756PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.
    Hwang ES, Kim GH (2007) Biomarkers for oxidative stress status of DNA, lipids, and proteins in vitro and in vivo cancer research. Toxicology 229:1–10PubMedCrossRefGoogle Scholar
  43. 43.
    Li JH, Rossman TG (1989) Mechanism of comutagenesis of sodium arsenite with n-methyl-n-nitrosourea. Biol Trace Elem Res 21:373–381PubMedCrossRefGoogle Scholar
  44. 44.
    Zhao CQ, Young MR, Diwan BA, Coogan TP, Waalkes MP (1997) Association of arsenic-induced malignant transformation with DNA hypomethylation and aberrant gene expression. Proc Natl Acad Sci U S A 94:10907–10912PubMedCentralPubMedCrossRefGoogle Scholar
  45. 45.
    Dizik M, Christman JK, Wainfan E (1991) Alterations in expression and methylation of specific gene in livers of rats fed a cancer promoting methyl-deficient diet. Carcinogenesis 12(Suppl 7):1307–1312PubMedCrossRefGoogle Scholar
  46. 46.
    Christman JK, Sheikhnejad G, Dizik M, Abileah S, Wainfan E (1993) Reversibility of changes in nucleic acid methylation and gene expression induced in rat liver by severe dietary deficiency. Carcinogenesis 14(Suppl 4):551–557PubMedCrossRefGoogle Scholar
  47. 47.
    Hsieh LL, Wainfan E, Hoshina S, Dizik M, Weinstein IB (1989) Altered expression of retrovirus-like sequences and cellular oncogenes in mice fed methyl-deficient diets. Cancer Res 49:3795–3799PubMedGoogle Scholar
  48. 48.
    Mass MJ, Wang L (1997) Arsenic alters cytosine methylation patterns of the promoter of the tumor suppressor gene p53 in human lung cells: a model for mechanism of carcinogenesis. Mutat Res 386:263–277PubMedCrossRefGoogle Scholar
  49. 49.
    Flora SJS, Bhadauria S, Kannan GM, Singh N (2007) Arsenic induced oxidative stress and the role of antioxidant supplementation during chelation: a review. J Environ Biol 28:333–347PubMedGoogle Scholar
  50. 50.
    Kannan GM, Flora SJS (2004) Chronic arsenic poisoning in the rats: treatment with combined administration of succimers and an antioxidants. Ecotoxicol Environ Saf 58:37–43PubMedCrossRefGoogle Scholar
  51. 51.
    Mishra D, Flora SJS (2008) Quercetin administration during chelation therapy protects arsenic-induced oxidative stress in mice. Biol Trace Elem Res 122(2):137–147PubMedCrossRefGoogle Scholar
  52. 52.
    Milton Prabu S, Muthumani M (2012) Silibinin ameliorates arsenic induced nephrotoxicity by abrogation of oxidative stress, inflammation and apoptosis in rats. Mol Biol Rep 39:11201–11216PubMedCrossRefGoogle Scholar
  53. 53.
    Mershiba SD, Dassprakash MV, Saraswathy SD (2013) Protective effect of naringenin on hepatic and renal dysfunction and oxidative stress in arsenic intoxicated rats. Mol Biol Rep 40:3681–3691PubMedCrossRefGoogle Scholar
  54. 54.
    Kaur H, Mishra D, Bhatnagar P, Kaushik P, Flora SJS (2009) Co-administration of α-lipoic acid and vitamin C protects liver and brain oxidative stress in mice exposed to arsenic contaminated water. Water Qual Expo Health 1:135–144CrossRefGoogle Scholar
  55. 55.
    Halliwell B (2006) Reactive species and antioxidants. Redox biology is a fundamental theme of aerobic life. Plant Physiol 141:312–322PubMedCentralPubMedCrossRefGoogle Scholar
  56. 56.
    Pant H, Rao MV (2010) In vitro melatonin supplementation against genetic toxicity by arsenic and fluoride. Adv Biores 1(2):17–24Google Scholar
  57. 57.
    Singh MK, Yadav SS, Gupta V, Khattri S (2013) Immunomodulatory role of Emblica officinalis in arsenic induced oxidative damage and apoptosis in thymocytes of mice. BMC Complement Alternat Med 13:193CrossRefGoogle Scholar
  58. 58.
    Balakumar BS, Ramanathan K, Kumaresan S, Suresh R (2010) DNA damage by sodium arsenite in experimental rats: ameliorative effects of antioxidant vitamins C and E. Indian J Sci Technol 3(3):322–327Google Scholar
  59. 59.
    Muthumani M (2013) Tetrahydrocurcumin potentially attenuates arsenic induced oxidative hepatic dysfunction in rats. J Clin Toxicol 3, 168. doi: 10.4172/2161-0495.1000168 Google Scholar
  60. 60.
    Winship KA (1984) Toxicity of inorganic arsenic salts. Adverse Drug React Acute Poisoning Rev 3:129–160PubMedGoogle Scholar
  61. 61.
    Mandal BK, Chowdhury TR, Samanta G et al (1996) Arsenic in groundwater in seven districts of west Bengal, India: the biggest arsenic calamity in the world. Curr Sci 70:976–986Google Scholar
  62. 62.
    Rahman M, Vahter M, Wahed MA et al (2006) Prevalence of arsenic exposure and skin lesions. A population based survey in Matlab, Bangladesh. J Epidemiol Community Health 60:242–248PubMedCentralPubMedCrossRefGoogle Scholar
  63. 63.
    Hunter FT, Kip AF, Irvine W (1942) Radioactive tracer studies on arsenic injected as potassium arsenite. J Pharmacol Exp Ther 76:207Google Scholar
  64. 64.
    NIOSH (1984) National Occupational Exposure Survey (1980–1983). Department of Health and Human Services. National Institute for Occupational Safety and Health, Cincinnati, OHGoogle Scholar
  65. 65.
    Lansdown AB (1995) Physiological and toxicological changes in the skin resulting from the action and interaction of metal ions. Crit Rev Toxicol 25:397–462PubMedCrossRefGoogle Scholar
  66. 66.
    Luchtrath H (1983) The consequences of chronic arsenic poisoning among Moselle wine growers. Pathoanatomical investigations of post-mortem examinations performed between 1960 and 1977. J Cancer Res Clin Oncol 105:173–182PubMedCrossRefGoogle Scholar
  67. 67.
    Philipp R (1985) Arsenic exposure: health effects and the risk of cancer. Rev Environ Health 5:27–57PubMedGoogle Scholar
  68. 68.
    Yamauchi H, Yamamura Y (1983) Concentration and chemical species of arsenic in human tissue. Bull Environ Contam Toxicol 31:267–270PubMedCrossRefGoogle Scholar
  69. 69.
    Lindgren A, Vahter M, Dencker L (1982) Autoradiographic studies on the distribution of arsenic in mice and hamsters administered 74As-arsenite or -arsenate. Acta Pharmacol Toxicol (Copenh) 51:253–265CrossRefGoogle Scholar
  70. 70.
    Longnecker MP, Daniels JL (2001) Environmental contaminants as etiologic factors for diabetes. Environ Health Perspect 109(Suppl 6):871–876PubMedCentralPubMedCrossRefGoogle Scholar
  71. 71.
    Tseng CH, Tseng CP, Chiou HY, Hsueh YM, Chong CK, Chen CJ (2002) Epidemiologic evidence of diabetogenic effect of arsenic. Toxicol Lett 133:69–76PubMedCrossRefGoogle Scholar
  72. 72.
    Wang A, Holladay SD, Wolf DC, Ahmed SA, Robertson JL (2006) Reproductive and developmental toxicity of arsenic in rodents: a review. Int J Toxicol 25:319–331PubMedCrossRefGoogle Scholar
  73. 73.
    Sarkar M, Chaudhuri GR, Chattopadhyay A, Biswas NM (2003) Effect of sodium arsenite on spermatogenesis, plasma gonadotrophins and testosterone in rats. Asian J Androl 5:27–31PubMedGoogle Scholar
  74. 74.
    Aposhian HV (1996) Arsenic toxicology: does methylation of arsenic species have an evolutionary significance? Met Ions Biol Med 4:399–401Google Scholar
  75. 75.
    Kitchin KT (2001) Recent advances in arsenic carcinogenesis: modes of action, animal model systems, and methylated arsenic metabolites. Toxicol Appl Pharmacol 172:249–261PubMedCrossRefGoogle Scholar
  76. 76.
    Basu A, Ghosh P, Das JK, Banerjee A, Ray K, Giri AK (2004) Micronuclei as biomarkers of carcinogen exposure in populations exposed to arsenic through drinking water in west Bengal, India: a comparative study in three cell types. Cancer Epidemiol Biomarkers Prev 13:820–827PubMedGoogle Scholar
  77. 77.
    Wegner R, Radon K, Heinrich-Ramm R, Seemann B, Riess A, Koops F, Poschadel B, Szadkowski D (2004) Biomonitoring results and cytogenetic markers among harbour workers with potential exposure to river silt aerosols. Occup Environ Med 61:247–253PubMedCentralPubMedCrossRefGoogle Scholar
  78. 78.
    Chen CJ, Hsu LI, Wang CH, Shih WL et al (2005) Biomarkers of exposure, effect, and susceptibility of arsenic-induced health hazards in Taiwan. Toxicol Appl Pharmacol 206:198–206PubMedCrossRefGoogle Scholar
  79. 79.
    Martinez V, Creus A, Venegas W, Arroyo A, Beck JP, Gebel TW, Surralles J, Marcos R (2005) Micronuclei assessment in buccal cells of people environmentally exposed to arsenic in northern Chile. Toxicol Lett 155:319–327PubMedCrossRefGoogle Scholar
  80. 80.
    Ramirez T, Garcia-Montalvo V, Wise C, Cea-Olivares R, Poirier LA, Herrera LA (2003) S-adenosyl-L-methionine is able to reverse micronucleus formation induced by sodium arsenite and other cytoskeleton disrupting agents in cultured human cells. Mutat Res 528:61–74PubMedCrossRefGoogle Scholar
  81. 81.
    Dopp E, Hartmann LM, Florea AM, Von Recklinghausen U, Pieper R, Shokouhi B, Rettenmeier AW, Hirner AV, Obe G (2004) Uptake of inorganic and organic derivatives of arsenic associated with induced cytotoxic and genotoxic effects in Chinese hamster ovary (CHO) cells. Toxicol Appl Pharmacol 201:156–165PubMedCrossRefGoogle Scholar
  82. 82.
    Colognato R, Coppede F, Ponti J, Sabbioni E, Migliore L (2007) Genotoxicity induced by arsenic compounds in peripheral human lymphocytes analysed by cytokinesis-block micronucleus assay. Mutagenesis 22:255–261PubMedCrossRefGoogle Scholar
  83. 83.
    Mahata J, Ghosh P, Sarkar JN, Ray K, Natarajan AT, Giri AK (2004) Effect of sodium arsenite on peripheral lymphocytes in vitro: individual susceptibility among a population exposed to arsenic through the drinking water. Mutagenesis 19(3):223–229PubMedCrossRefGoogle Scholar
  84. 84.
    Yih LH, Lee TC (2000) Arsenite induces p53 accumulation through an ATM-dependent pathway in human fibroblasts. Cancer Res 60:6346–6352PubMedGoogle Scholar
  85. 85.
    Vuyyuri SB, Ishaq M, Kuppala D, Grover P, Ahuja YR (2006) Evaluation of micronucleus frequencies and DNA damage in glass workers exposed to arsenic. Environ Mol Mutagen 47:562–570PubMedCrossRefGoogle Scholar
  86. 86.
    Ding W, Hudson LG, Liu KJ (2005) Inorganic arsenic compounds cause oxidative damage to DNA and protein by inducing ROS and RNS generation in human keratinocytes. Mol Cell Biochem 279:105–112PubMedCrossRefGoogle Scholar
  87. 87.
    Ahmed K, Akhand AA, Hasan M, Islam M, Hasan A (2008) Toxicity of arsenic (sodium arsenite) to fresh water spotted snakehead Channa punctatus (Bloch) on cellular death and DNA content. Am-Euras J Agric Environ Sci 4(1):18–22Google Scholar
  88. 88.
    Partridge MA, Huang SXL, Hernandez-Rosa E, Davidson MM, Hei TK (2007) Arsenic induced mitochondrial DNA damage and altered mitochondrial oxidative function: implications for genotoxic mechanisms in mammalian cells. Cancer Res 67:5239–5247PubMedCrossRefGoogle Scholar
  89. 89.
    Huang SC, Lee TC (1998) Arsenite inhibits mitotic division and perturbs spindle dynamics in HeLa S3 cells. Carcinogenesis 19:889–896PubMedCrossRefGoogle Scholar
  90. 90.
    Nakamuro K, Sayato T (1981) Comparative studies of chromosomal aberration induced by trivalent and pentavalent arsenic. Mutat Res 88:73–80PubMedCrossRefGoogle Scholar
  91. 91.
    Nordenson I, Sweins A, Beckman L (1981) Chromosome aberrations in cultured human lymphocytes exposed to trivalent and pentavalent arsenic. Scand J Work Environ Health 7:277–281PubMedCrossRefGoogle Scholar
  92. 92.
    Schwerdtle T, Walter I, Mackiw I, Hartwig A (2003) Induction of oxidative DNA damage by arsenite and its trivalent and pentavalent methylated metabolites in cultured human cells and isolated DNA. Carcinogenesis 24(5):967–974PubMedCrossRefGoogle Scholar
  93. 93.
    Sordo M, Herrera LA, Ostrosky-Wegman P, Rojas E (2001) Cytotoxic and genotoxic effects of As, MMA, and DMA on leukocytes and stimulated human lymphocytes. Teratog Carcinog Mutagen 21:249–260PubMedCrossRefGoogle Scholar
  94. 94.
    Wang TS, Hsu TY, Chung CH, Wang AS, Bau DT, Jan KY (2001) Arsenite induces oxidative DNA adducts and DNA-protein cross-links in mammalian cells. Free Radic Biol Med 31:321–330PubMedCrossRefGoogle Scholar
  95. 95.
    Dong JT, Luo XM (1993) Arsenic-induced DNA-strand breaks associated with DNA-protein crosslinks in human fetal lung fibroblasts. Mutat Res 302:97–102PubMedCrossRefGoogle Scholar
  96. 96.
    Ramirez P, Del Razo LM, Gutierrez-Ruiz MC, Gonsebatt ME (2000) Arsenite induces DNA-protein crosslinks and cytokeratin expression in the WRL-68 human hepatic cell line. Carcinogenesis 21:701–706PubMedCrossRefGoogle Scholar
  97. 97.
    Pierce BL, Kibriya MG, Tong L, Jasmine F et al (2012) Genome-wide association study identifies chromosome 10q24.32 variants associated with arsenic metabolism and toxicity phenotypes in Bangladesh. PLoS Genet 8, e1002522. doi: 10.1371/journal.pgen.1002522 PubMedCentralPubMedCrossRefGoogle Scholar
  98. 98.
    Helleday T, Nilsson R, Jenssen D (2000) Arsenic[III] and heavy metal ions induce intrachromosomal homologous recombination in the hprt gene V79 Chinese hamster cells. Environ Mol Mutagen 35:114–122PubMedCrossRefGoogle Scholar
  99. 99.
    Mass MJ, Tennant A, Roop BC, Cullen WR, Styblo M, Thomas DJ, Kligerman AD (2001) Methylated trivalent arsenic species are genotoxic. Chem Res Toxicol 14:355–361PubMedCrossRefGoogle Scholar
  100. 100.
    Petrick JS, Ayala-Fierro F, Cullen WR, Carter DE, Vasken Aposhian H (2000) Monomethylarsonous acid (MMA(III)) is more toxic than arsenite in Chang human hepatocytes. Toxicol Appl Pharmacol 163:203–207PubMedCrossRefGoogle Scholar
  101. 101.
    Petrick JS, Jagadish B, Mash EA, Aposhian HV (2001) Monomethylarsonous acid (MMAIII) and arsenite: LD50 in hamsters and in vitro inhibition of pyruvate dehydrogenase. Chem Res Toxicol 14:651–656PubMedCrossRefGoogle Scholar
  102. 102.
    Styblo M, Del Razo LM, Vega L, Germolec DR, LeCluyse EL, Hamilton GA, Reed W, Wang C, Cullen WR, Thomas DJ (2000) Comparative toxicity of trivalent and pentavalent inorganic and methylated arsenicals in rat and human cells. Arch Toxicol 74:289–299PubMedCrossRefGoogle Scholar
  103. 103.
    Andrew AS, Karagas MR, Hamilton JW (2003) Decreased DNA repair gene expression among individuals exposed to arsenic in United States drinking water. Int J Cancer 104:263–268PubMedCrossRefGoogle Scholar
  104. 104.
    Li JH, Rossman TG (1989) Inhibition of DNA ligase activity by arsenite: a possible mechanism of its comutagenesis. Mol Toxicol 2:1–9PubMedGoogle Scholar
  105. 105.
    Bencko V, Wagner V, Wagnerova M, Botora J (1988) Immunological profiles in workers of a power plant burning coal rich in arsenic content. J Hyg Epidemiol Microbiol Immunol 32:137–147PubMedGoogle Scholar
  106. 106.
    Nordenson I, Salmonsson S, Brun E, Bechman G (1978) Occupational and environmental risks in and around a smelter in northern Sweden. II. Chromosomal aberrations in workers exposed to arsenic. Hereditas 88:47–50PubMedCrossRefGoogle Scholar
  107. 107.
    Rossman TG, Meyn MS, Troll W (1977) Effects of arsenic on DNA repair in Escherichia coli. Environ Health Perspect 19:229–233PubMedCentralPubMedCrossRefGoogle Scholar
  108. 108.
    Sinha D, Roy M (2011) Antagonistic role of tea against sodium arsenite-induced oxidative DNA damage and inhibition of DNA repair in Swiss albino mice. J Environ Pathol Toxicol Oncol 30:311–322PubMedCrossRefGoogle Scholar
  109. 109.
    Valenzuela OL, Borja-Aburto VH, Garcia-Vargas GG, Cruz-Gonzalez MB, Garcia-Montalvo EA, Calderon-Aranda ES, Del Razo LM (2005) Urinary trivalent methylated arsenic species in a population chronically exposed to inorganic arsenic. Environ Health Perspect 113:250–254PubMedCentralPubMedCrossRefGoogle Scholar
  110. 110.
    Drobna Z, Naranmandura H, Kubachka KM, Edwards BC, Herbin-Davis K, Styblo M, Le XC, Creed JT, Maeda N, Hughes MF, Thomas DJ (2009) Disruption of the arsenic (+3 oxidation state) methyltransferase gene in the mouse alters the phenotype for methylation of arsenic and affects distribution and retention of orally administered arsenate. Chem Res Toxicol 22:1713–1720PubMedCentralPubMedCrossRefGoogle Scholar
  111. 111.
    Hall AH (2002) Chronic arsenic poisoning. Toxicol Lett 128:69–72PubMedCrossRefGoogle Scholar
  112. 112.
    Naranmandura H, Suzuki N, Suzuki KT (2006) Trivalent arsenicals are bound to proteins during reductive methylation. Chem Res Toxicol 19:1010–1018. doi: 10.1021/tx060053f PubMedCrossRefGoogle Scholar
  113. 113.
    Suzuki KT, Mandal BK, Ogra Y (2002) Speciation of arsenic in body fluids. Talanta 58:111–119. doi: 10.1016/ S0039-9140(02)00260-6 PubMedCrossRefGoogle Scholar
  114. 114.
    Garcia-Shavez E, Jimenez I, Segura B, Razo LMD (2006) Lipid peroxidative damage and distribution of inorganic and its metabolite in the rat nervous system after arsenite exposure: influence of alpha tocopherol. Neurotoxicology 27:1024–1031CrossRefGoogle Scholar
  115. 115.
    Kessel M, Liu SX, Xu A, Santella R, Hei TK (2002) Arsenic induces oxidative DNA damage in mammalian cells. Mol Cell Biochem 234(235):301–308PubMedCrossRefGoogle Scholar
  116. 116.
    Flora SJ (2011) Arsenic-induced oxidative stress and its reversibility. Free Radic Biol Med 51:257–281PubMedCrossRefGoogle Scholar
  117. 117.
    Herman JG, Merlo A, Mao L, Lapidus RG, Issa JPJ, Davidson NE (1995) Inactivation of the CDKN2/p16/MTS1 gene is frequently associated with aberrant DNA methylation in all common human cancers. Cancer Res 55:4525–30PubMedGoogle Scholar
  118. 118.
    Aggarwal BB, Bhardwaj A, Aggarwal RS, Seeram NP, Shishodia S, Takada Y (2004) Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies. Anticancer Res 24(5A):2783–2840PubMedGoogle Scholar
  119. 119.
    Chen C, Jiang X, Hu Y, Zhang Z (2013) The protective role of resveratrol in the sodium arsenite-induced oxidative damage via modulation of intracellular GSH homeostasis. Biol Trace Elem Res 155:119–131PubMedCrossRefGoogle Scholar
  120. 120.
    Singh N, Kumari D (2013) Amelioration of genotoxicity by papaya extract induced by arsenic contaminated drinking water. Biogeosciences 8(2):623–626Google Scholar
  121. 121.
    Manna P, Sinha M, Sil PC (2007) Protection of arsenic-induced hepatic disorder by arjunolic acid. Basic Clin Pharmacol Toxicol 101:333–338PubMedCrossRefGoogle Scholar
  122. 122.
    Acharyya N, Ali SS, Deb B, Chattopadhyay S, Maiti S (2014) Green tea (Camellia sinensis) alleviates arsenic-induced damages to DNA and intestinal tissues in rat and in situ intestinal loop by reinforcing antioxidant system. Environ Toxicol. doi: 10.1002/tox PubMedGoogle Scholar
  123. 123.
    Zhu QY, Chen ZY (1999) Isolation and analysis of green tea polyphenols by HPLC. Anal Lab 18:70–72Google Scholar
  124. 124.
    Bhattacharya S, Haldar PK (2012) Ameliorative effect Trichosanthes dioica root against arsenic-induced brain toxicity in albino rats. Toxicol Environ Chem 94(4):769–778CrossRefGoogle Scholar
  125. 125.
    Bhattacharya S, Haldar PK (2012) Trichosanthes dioica fruit ameliorates experimentally induced arsenic toxicity in male albino rats through the alleviation of oxidative stress. Biol Trace Elem Res 148:232–241PubMedCrossRefGoogle Scholar
  126. 126.
    Chopra RN, Nayar SL, Chopra IC (2002) Glossary of Indian medicinal plants, 1st edn. CSIR, New Delhi, pp 340–1Google Scholar
  127. 127.
    Ghaisas MM, Tanwar MB, Ninave PB, Navghare VV, Deshpande AD (2008) Hepatoprotective activity of aqueous and ethanolic extract of Trichosanthes dioica Roxb. in ferrous sulphate induced liver injury. Pharmacologyonline 3:127–35Google Scholar
  128. 128.
    Maiti S, Chattopadhyay S, Acharyya N, Deb B, Hati AK (2014) Emblica officinalis (amla) ameliorates arsenic induced liver damage via DNA protection by antioxidants systems. Mol Cell Toxicol 10:75–82CrossRefGoogle Scholar
  129. 129.
    Khan KH (2009) Roles of Emblica officinalis in medicine—a review. Bot Res Int 2(4):218–28Google Scholar
  130. 130.
    Habib-ur-Rehman YKA, Choudhary MA, Khaliq N, Atta-ur-Rahman CMI, Malik S (2007) Studies on the chemical constituents of Phyllanthus emblica. Nat Prod Res 21:775–81PubMedCrossRefGoogle Scholar
  131. 131.
    Krishnaveni M, Mirunalini S (2010) Therapeutic potential of Phyllanthus emblica (amla): the ayurvedic wonder. J Basic Clin Physiol Pharmacol 21:93–105PubMedGoogle Scholar
  132. 132.
    Chattopadhyay S, Maiti S, Maji G, Deb B, Pan B, Ghosh D (2011) Protective role of Moringa oleifera (Sajina) seed on arsenic-induced hepatocellular degeneration in female albino rats. Biol Trace Elem Res 142:200–212PubMedCrossRefGoogle Scholar
  133. 133.
    Singh BN, Singh BR, Singh RL, Prakash D, Dhakarey R, Upadhyay G, Singh HB (2009) Oxidative DNA damage protective activity, antioxidant and anti-quorum sensing potentials of Moringa oleifera. Food Chem Toxicol 47:1109–1116PubMedCrossRefGoogle Scholar
  134. 134.
    Bajpai M, Pande A, Tewari SK, Prakash D (2005) Phenolic contents and antioxidant activity of some food and medicinal plants. Int J Food Sci Nutr 56:287–291PubMedCrossRefGoogle Scholar
  135. 135.
    Siddhuraju P, Becker K (2003) Antioxidant properties of various solvent extracts of total phenolic constituents from three different agroclimatic origins of drumstick tree (Moringa oleifera Lam.) leaves. J Agric Food Chem 51:2144–2155PubMedCrossRefGoogle Scholar
  136. 136.
    Milton Prabu S, Sumedha NC (2014) Ameliorative effect of diallyl trisulphide on arsenic-induced oxidative stress in rat erythrocytes and DNA damage in lymphocytes. J Basic Clin Physiol Pharmacol 25(2):181–197Google Scholar
  137. 137.
    Shankar S, Singh G, Srivastava RK (2007) Chemoprevention by resveratrol: molecular mechanisms and therapeutic potential. Front Biosci 12:4839–4854PubMedCrossRefGoogle Scholar
  138. 138.
    Kadirvel R, Sundaram K, Mani S et al (2007) Supplementation of ascorbic acid and α-tocopherol prevents arsenic-induced protein oxidation and DNA damage induced by arsenic in rats. Hum Exp Toxicol 26:939–946PubMedCrossRefGoogle Scholar
  139. 139.
    Kelly SA, Havrilla CHM, Brady TC, Abramo KH, Levin ED (1998) Oxidative stress in toxicology: established mammalian and emerging piscine model systems. Environ Health Perspect 106:375–384PubMedCentralPubMedCrossRefGoogle Scholar
  140. 140.
    Yamanaka K, Hasegawa A, Sawamura R, Okada S (1991) Cellular response to oxidative damage in lung induced by the administration of dimethylarsinic acid, a major metabolite of inorganic arsenics, in mice. Toxicol Appl Pharmacol 108:205–213PubMedCrossRefGoogle Scholar
  141. 141.
    Acharyya N, Chattopadhyay S, Maiti S (2014) Chemoprevention against arsenic-induced mutagenic DNA breakage and apoptotic liver damage in rat via antioxidant and SOD1 upregulation by green tea (Camellia sinensis) which recovers broken DNA resulted from arsenic-H2O2 related in vitro oxidant stress. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 32(4):338–361. doi: 10.1080/10590501.2014.967061 PubMedCrossRefGoogle Scholar
  142. 142.
    Aposhian HV, Zakharyan RA, Avram MD, Kopplin MJ, Wollenberg ML (2003) Oxidation and detoxification of trivalent arsenic species. Toxicol Appl Pharmacol 193:1–8PubMedCrossRefGoogle Scholar
  143. 143.
    Masella R, Di Benedetto R, Vari R, Filesi C, Giovannini C (2005) Novel mechanisms of natural antioxidant compounds in biological systems: involvement of glutathione and glutathione-related enzymes. J Nutr Biochem 16:577–586PubMedCrossRefGoogle Scholar
  144. 144.
    Afzal M, Afzal A, Jones A, Armstrong D (2002) A rapid method for the quantification of GSH and GSSG in biological samples. Methods Mol Biol 186:117–122PubMedGoogle Scholar
  145. 145.
    Manna P, Sinha M, Sil PC (2008) Arsenic-induced oxidative myocardial injury: protective role of arjunolic acid. Arch Toxicol 82:137–149PubMedCrossRefGoogle Scholar
  146. 146.
    Aposhian HV (1989) Biochemical toxicology of arsenic. Rev Biochem Toxicol 10:265–99Google Scholar
  147. 147.
    Radabaugh TR, Aposhian HV (2000) Enzymatic reduction of arsenic compounds in mammalian systems: reduction of arsenate to arsenite by human liver arsenate reductase. Chem Res Toxicol 13:26–30PubMedCrossRefGoogle Scholar
  148. 148.
    Exner R, Wessner B, Manhart N, Roth E (2000) Therapeutic potential of glutathione. Wien Klin Wochenschr 112:610–616PubMedGoogle Scholar
  149. 149.
    Hayakawa T, Kobayashi Y, Cui X, Hirano S (2005) A new metabolic pathway of arsenite: arsenite-glutathione complexes are substrates for human arsenic methyltransferase Cyt19. Arch Toxicol 79(4):183–191PubMedCrossRefGoogle Scholar
  150. 150.
    Eder E, Wacker M, Lutz U, Nair J, Fang X, Bartsch H, Beland FA, Schlatter J, Lutz WK (2006) Oxidative stress related DNA adducts in the liver of female rats fed with sunflower-, rapeseed-, olive- or coconut oil supplemented diets. Chem Biol Interact 159:81–89PubMedCrossRefGoogle Scholar
  151. 151.
    Kalia K, Narula GD, Kannan GM, Flora SJS (2007) Effects of combined administration of captopril and DMSA on arsenite induced oxidative stress and blood and tissue arsenic concentration in rats. Comp Biochem Physiol C Toxicol Pharmacol 144(4):372–379PubMedCrossRefGoogle Scholar
  152. 152.
    Bhadauria S, Flora SJS (2004) Arsenic induced inhibition of δ-aminolevulinate dehydratase activity in rat blood and its response to meso-2,3-dimercaptosuccinic acid and monoisoamyl DMSA. Biomed Environ Sci 17:101–108PubMedGoogle Scholar
  153. 153.
    Flora SJS, Saxena G, Mehta A (2007) Reversal of lead-induced neuronal apoptosis by chelation treatment in rats: role of reactive oxygen species and intracellular Ca2+. J Pharmacol Exp Ther 322:108–116PubMedCrossRefGoogle Scholar
  154. 154.
    Singh S, Rana SVS (2007) Amelioration of arsenic toxicity by L-ascorbic acid in laboratory rat. J Environ Biol 28(2):377–384PubMedGoogle Scholar
  155. 155.
    Sumedha NC, Milton Prabu S (2013) Arsenic induced oxidative hematotoxicity in rats and its protection by diallyl trisulfide. Int J Biol Pharm Res 4(7):507–515Google Scholar
  156. 156.
    Wang ZG, Rivi R, Delva L et al (1998) Arsenic trioxide and melarsoprol induce programmed cell death in myeloid leukemia cell lines and function in a PML and PML-RARα independent manner. Blood 92(5):1497–1504PubMedGoogle Scholar
  157. 157.
    Dong Z (2002) The molecular mechanisms of arsenic-induced cell transformation and apoptosis. Environ Health Perspect 110(Suppl 5):757–759PubMedCentralPubMedCrossRefGoogle Scholar
  158. 158.
    Kadirvel R, Muthuswamy A, Samuel S, Panneerselvam C (2005) Ascorbic acid and α-tocopherol as potent modulators of apoptosis on arsenic induced toxicity in rats. Toxicol Lett 156(2):297–306CrossRefGoogle Scholar
  159. 159.
    Chen NY, Ma WY, Yang CS, Dong Z (2000) Inhibition of arsenite-induced apoptosis and AP-1 activity by epigallocatechin-3-gallate and theaflavins. J Environ Pathol Toxicol Oncol 19(3):287–295PubMedGoogle Scholar
  160. 160.
    Flora SJS (2002) Nutritional components modify metal absorption, toxic response and chelation therapy. J Nutr Environ Med 12(1):53–67CrossRefGoogle Scholar
  161. 161.
    Mishra D, Gupta R, Pant SC, Kushwah P, Satish HT, Flora SJS (2009) Co-administration of monoisoamyl dimercaptosuccinic acid and Moringa oleifera seed powder protects arsenic-induced oxidative stress and metal distribution in mice. Toxicol Mech Methods 19(2):169–182PubMedCrossRefGoogle Scholar
  162. 162.
    Flora SJS, Chouhan S, Kannan GM, Mittal M, Swarnakar H (2008) Combined administration of taurine and monoisoamyl DMSA protects arsenic induced oxidative injury in rats. Oxidative Med Cell Longev 1(1):39–45CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Guru Jambhehswar University of Science and TechnologyHisarIndia

Personalised recommendations