Recent advances in arsenic carcinogenesis: modes of action, animal model systems, and methylated arsenic metabolites.
By K. Kitchin. Toxicology and Applied Pharmacology, 2001
792 citations recorded by the source corpus.
Recent advances in our knowledge of arsenic carcinogenesis include the development of rat or mouse models for all human organs in which inorganic arsenic is known to cause cancer-skin, lung, urinary bladder, liver, and kidney. Tumors can be produced from either promotion of carcinogenesis protocols (mouse skin and lungs, rat bladder, kidney, liver, and thyroid) or from complete carcinogenesis protocols (rat bladder and mouse lung). Experiments with p53(+/-) and K6/ODC transgenic mice administered dimethylarsinic acid or arsenite have shown some degree of carcinogenic, cocarcinogenic, or promotional activity in skin or bladder. At present, with the possible exception of skin, the arsenic carcinogenesis models in wild-type animals are more highly developed than in transgenic mice. Recent advances in arsenic metabolism have suggested that methylation of inorganic arsenic may be a toxification, rather than a detoxification, pathway and that trivalent methylated arsenic metabolites, particularly monomethylarsonous acid and dimethylarsinous acid, have a great deal of biological activity. Accumulating evidence indicates that these trivalent, methylated, and relatively less ionizable arsenic metabolites may be unusually capable of interacting with cellular targets such as proteins and even DNA. In risk assessment of environmental arsenic, it is important to know and to utilize both the mode of carcinogenic action and the shape of the dose-response curve at low environmental arsenic concentrations. Although much progress has been recently made in the area of arsenic's possible mode(s) of carcinogenic action, a scientific concensus has not yet been reached. In this review, nine different possible modes of action of arsenic carcinogenesis are presented and discussed-induced chromosomal abnormalities, oxidative stress, altered DNA repair, altered DNA methylation patterns, altered growth factors, enhanced cell proliferation, promotion/progression, gene amplification, and suppression of p53.
Subfields: Cancer Research, Environmental Chemistry, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/c35af0966f14f6ffb4b76a8f63f258589138f65e
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Citations in the corpus
- Arsenic exposure and toxicology: a historical perspective. (2011, background): “Reactive species are formed in vitro and in vivo in the presence of arsenic and include superoxide anion, hydroxyl radical, hydrogen peroxide, reactive nitrogen species, and arsenic-centered and arsenic peroxyl radicals (Kitchin 2001; Shi et al., 2004).”
- Aquatic arsenic: toxicity, speciation, transformations, and remediation. (2009, background): “The toxicity of DMMTAV may be caused by the production of reactive oxygen species (ROS) during its exposure, which may cause mutagenesis and DNA damage, initiating cancer (Kitchin, 2001).”
- Arsenic: toxicity, oxidative stress and human disease (2011, background): “DMA causes several genotoxic effects, including single strand DNA breaks, the formation of apurinic and apyrimidinic sites, an enhancement in oxidative stress as documented by oxidation of DNA bases, formation of DNA–protein crosslinks and chromosomal aberrations (Kitchin, 2001).”
- Human Health Effects From Chronic Arsenic Poisoning–A Review (2006, background): “[7] Several review articles have also been published, including Yoshida et al.,[8] Luster and Simeonova,[9] Watanabe,[10] Tchounwou et al.,[11] Rossman et al.,[12] Mahata et al.,[13] Kitchin,[14] and Ratnaike.”