Inorganic arsenic: A non-genotoxic carcinogen

Samuel Monroe Cohen, Aparajita Chowdhury, Lora L Arnold

Research output: Contribution to journalReview article

28 Citations (Scopus)

Abstract

Inorganic arsenic induces a variety of toxicities including cancer. The mode of action for cancer and non-cancer effects involves the metabolic generation of trivalent arsenicals and their reaction with sulfhydryl groups within critical proteins in various cell types which leads to the biological response. In epithelial cells, the response is cell death with consequent regenerative proliferation. If this continues for a long period of time, it can result in an increased risk of cancer. Arsenicals do not react with DNA. There is evidence for indirect genotoxicity in various in vitro and in vivo systems, but these involve exposures at cytotoxic concentrations and are not the basis for cancer development. The resulting markers of genotoxicity could readily be due to the cytotoxicity rather than an effect on the DNA itself. Evidence for genotoxicity in humans has involved detection of chromosomal aberrations, sister chromatid exchanges in lymphocytes and micronucleus formation in lymphocytes, buccal mucosal cells, and exfoliated urothelial cells in the urine. Numerous difficulties have been identified in the interpretation of such results, including inadequate assessment of exposure to arsenic, measurement of micronuclei, and potential confounding factors such as tobacco exposure, folate deficiency, and others. Overall, the data strongly supports a non-linear dose response for the effects of inorganic arsenic. In various in vitro and in vivo models and in human epidemiology studies there appears to be a threshold for biological responses, including cancer.

Original languageEnglish (US)
Pages (from-to)28-37
Number of pages10
JournalJournal of Environmental Sciences (China)
Volume49
DOIs
StatePublished - Nov 1 2016

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Carcinogens
Arsenic
carcinogen
Arsenicals
arsenic
cancer
Lymphocytes
genotoxicity
DNA
Epidemiology
Tobacco
Cell death
Cytotoxicity
Aberrations
Folic Acid
Toxicity
Proteins
epidemiology
tobacco
urine

Keywords

  • Arsenic
  • Cancer
  • Cell proliferation
  • Cytotoxicity
  • Genotoxicity
  • Regeneration

ASJC Scopus subject areas

  • Environmental Engineering
  • Environmental Chemistry
  • Environmental Science(all)

Cite this

Inorganic arsenic : A non-genotoxic carcinogen. / Cohen, Samuel Monroe; Chowdhury, Aparajita; Arnold, Lora L.

In: Journal of Environmental Sciences (China), Vol. 49, 01.11.2016, p. 28-37.

Research output: Contribution to journalReview article

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