Evaluation of the carcinogenicity of inorganic arsenic

@article{Cohen2013EvaluationOT,
  title={Evaluation of the carcinogenicity of inorganic arsenic},
  author={Samuel M. Cohen and Lora L. Arnold and Barbara D. Beck and Ari S. Lewis and Michal Eldan},
  journal={Critical Reviews in Toxicology},
  year={2013},
  volume={43},
  pages={711 - 752}
}
Abstract Inorganic arsenic (iAs) at high exposures is a human carcinogen, affecting mainly the urinary bladder, lung and skin. We present an assessment of the mode of action (MOA) of iAs’s carcinogenicity based on the United States Environmental Protection Agency/International Programme on Chemical Safety (USEPA/IPCS) framework, focusing primarily on bladder cancer. Evidence is presented for a MOA involving formation of reactive trivalent metabolites interacting with critical cellular… 

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References

SHOWING 1-10 OF 378 REFERENCES

Oral exposure to inorganic arsenic: evaluation of its carcinogenic and non-carcinogenic effects

TLDR
A tolerable daily dose, based on epidemiological studies on arsenic-induced skin disorders, is presented and is used to evaluate the reliability of existing cancer-risk assessments and to improve current assessments of non-cancer health effects.

Understanding arsenic carcinogenicity by the use of animal models.

Arsenic-induced bladder cancer in an animal model.

Methylated Arsenicals: The Implications of Metabolism and Carcinogenicity Studies in Rodents to Human Risk Assessment

TLDR
Using a margin-of-exposure approach for MMAV and DMAV risk assessment is appropriate and the evidence strongly supports a nonlinear dose-response relationship for the biologic processes involved in the carcinogenicity of arsenicals.

Further evidence against a direct genotoxic mode of action for arsenic-induced cancer.

Carcinogenicity of dimethylarsinic acid in male F344 rats and genetic alterations in induced urinary bladder tumors.

TLDR
DMA was demonstrated to be a carcinogen for the rat urinary bladder and suggested that DMA exposure may be relevant to the carcinogenic risk of inorganic arsenic in humans and diverse genetic alterations observed in DMA-induced urinary bladder tumors imply that multiple genes are involved in stages of D MA-induced tumor development.

Toxicological interactions among arsenic, cadmium, chromium, and lead in human keratinocytes.

TLDR
Initial data are consistent with the suggestion that synergistic cytotoxicity turned to antagonistic effects because at highest mixture exposure concentrations cellular defense mechanisms were enhanced.

Cancer in experimental animals exposed to arsenic and arsenic compounds

TLDR
This work reviews the available rodent studies considered relevant to carcinogenic assessment of arsenicals, taking advantage of the most recent review by the International Agency for Research on Cancer (IARC) that has not yet appeared as a full monograph but has been summarized.

Characterization of intracellular inclusions in the urothelium of mice exposed to inorganic arsenic.

TLDR
The urothelial cell inclusions induced by arsenicals appear to serve as a detoxifying sequestration mechanism similar to other metals, and they do not represent micronuclei.
...