Genotoxicity of arsenical compounds.
With respect to global human health hazard, arsenic (As) is one of the most important environmental single substance toxicants. Currently, millions of people all over the world are exposed to the ubiquitous element in exposure levels leading to long-term toxicity, in particular cancer. Unfortunately, it has not been elucidated up to now how As mechanistically leads to the induction of neoplasia. Besides its tumorigenic potential, As has been shown to be genotoxic in a wide variety of different experimental set-ups and biological endpoints. In vitro, the element was shown to induce chromosomal mutagenicity like micronuclei, chromosome aberrations, and sister chromatid exchanges. It mainly acts clastogenic but also has an aneugenic potential. Instead, its potential to induce point mutations is very low in bacterial as well as in mammalian cell systems. However, in combined exposure with point mutagens in vitro, As was shown to enhance the frequency of chemical mutations in a synergistic manner. Additionally, As was shown to induce chromosome aberrations and micronuclei in vivo in experiments with mice. After long-term exposure to As-contaminated drinking water, the great majority of human biomonitoring studies found elevated frequencies of DNA lesions like micronuclei or chromosome aberrations. Respective occupational studies are few. Like it is the case for As carcinogenicity, it is not known through which mechanism the genotoxicity of As is mediated, although the data available indicate that As may act indirectly on DNA, i.e. via mechanisms like interference of regulation of DNA repair or integrity. Because of the indirect mode of action, it has been discussed as well that As's genotoxicity may underlie a sublinear dose-response relationship. However, various problems like non-standardized test systems and experimental variability make it impossible to prove such statement. Basically, to be able to improve risk assessment, it is of crucial importance to scientifically approach the mechanistic way of induction of As's genotoxicity and carcinogenicity.
Gebel
T W
TW
Medical Institute of General Hygiene and Environmental Health, University of Goettingen, Windausweg 2, D-37073 Goettingen, Germany.
D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D020261:Arsenic Poisoning / Q000453:epidemiology* / Q000209:etiology; D004781:Environmental Exposure / Q000009:adverse effects; D014943:Global Health; D006801:Humans; D009152:Mutagenicity Tests
D001151:Arsenic