Comparative toxicity of trivalent and pentavalent inorganic and methylated arsenicals in rat and human cells

  title={Comparative toxicity of trivalent and pentavalent inorganic and methylated arsenicals in rat and human cells},
  author={Miroslav St{\'y}blo and Luz M. Del Razo and Libia Vega and Dori R. Germolec and Edward L. Lecluyse and Geraldine A. Hamilton and William Reed and Changqing Wang and William Cullen and David J. Thomas},
  journal={Archives of Toxicology},
Abstract. Biomethylation is considered a major detoxification pathway for inorganic arsenicals (iAs). According to the postulated metabolic scheme, the methylation of iAs yields methylated metabolites in which arsenic is present in both pentavalent and trivalent forms. Pentavalent mono- and dimethylated arsenicals are less acutely toxic than iAs. However, little is known about the toxicity of trivalent methylated species. In the work reported here the toxicities of iAs and trivalent and… 
Methylated Arsenicals: The Implications of Metabolism and Carcinogenicity Studies in Rodents to Human Risk Assessment
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.
Cellular uptake, subcellular distribution and toxicity of arsenic compounds in methylating and non-methylating cells.
The correlation of uptake with toxicity indicates a significant role of membrane permeability towards toxicity, and cytotoxic effects are more distinct in hepatocytes, which is needed to define the implications of the observed enrichment of arsenic in specific cellular organelles for its carcinogenic activity.
Mechanisms of arsenic biotransformation.
There are indications that subjects with low MMA in urine have faster elimination of ingested arsenic, compared to those with more MMA in pee, and to what extent MMA( III) and DMA(III) contribute to the observed toxicity following exposure to inorganic arsenic remains to be elucidated.
The cellular metabolism and systemic toxicity of arsenic.
The current knowledge of the processes that control the formation and fate of the methylated metabolites of arsenic and of the biological effects of these compounds are summarized.
Arsenic metabolism and thioarsenicals.
It is concluded that the methylation reaction takes place with simultaneous reductive rather than stepwise oxidative methylation, and production of pentavalent methylated arsenic metabolites are suggested to be as the end product of metabolism, rather than intermediates.
Urinary Trivalent Methylated Arsenic Species in a Population Chronically Exposed to Inorganic Arsenic
Chronic exposure to inorganic arsenic (iAs) has been associated with increased risk of various forms of cancer and of noncancerous diseases. Metabolic conversions of iAs that yield highly toxic and
Arsenic toxicity and potential mechanisms of action.
  • M. Hughes
  • Chemistry, Medicine
    Toxicology letters
  • 2002
A better understanding of the mechanism(s) of action) of arsenic will make a more confident determination of the risks associated with exposure to this chemical.
Evidence for toxicity differences between inorganic arsenite and thioarsenicals in human bladder cancer cells.
Compared with a previous study using human epidermoid carcinoma A431 cells, it is shown that iAs(III) was much less cytotoxic than DMMTA(V) (LC(50)=112 microM) in human bladder EJ-1 cells, suggesting that production of ROS was the main cause of cell death from exposure to DMM TA(V), but not iAs (III).
Forced uptake of trivalent and pentavalent methylated and inorganic arsenic and its cyto-/genotoxicity in fibroblasts and hepatoma cells.
The results show that organic and inorganic arsenicals are taken up to a higher degree by fibroblasts compared to hepatoma cells, and it may be hypothesized that the arsenic-induced genotoxic effects observed in fibro Blasts are due to the high uptake of arsenicals into this cell type.
Biomarkers of Exposure: A Case Study with Inorganic Arsenic
  • M. Hughes
  • Chemistry, Medicine
    Environmental health perspectives
  • 2006
Questions still remain, however, as to how reliably the measurement of urinary arsenic, either total or speciated, may predict arsenic concentrations at target tissues as well as how this measurement could be used to assess chronic exposures to iAs.