Acrylonitrile induction of rodent neoplasia: Potential mechanism of action and relevance to humans

Acrylonitrile, an industrial chemical, is a multisite carcinogen in rats and mice, producing tumors four tissues with barrier function, that is, brain, forestomach, Zymbal’s gland, Harderian gland. To assess mechanism(s) of action (MoA) for induction neoplasia to evaluate whether the findings rodents are indicative human hazard, data on potential key effects produced by acrylonitrile rodent target carcinogenicity were evaluated. A notable finding was depletion glutathione various organs, including two tissues, suggesting this effect could be critical initiating event. An additional combination oxidative DNA damage cytotoxic its metabolites, cyanide, 2-cyanoethylene oxide, initiate pro-inflammatory signaling sustained cell tissue injury, leading compensatory proliferation neoplastic development. The vivo DNA-binding genotoxicity has been studied several no compelling positive results. Thus, while some mutagenic reported acrylonitrile-exposed rodents, determine mutagenicity stems from direct reactivity insufficient. Accordingly, consistent primarily non-genotoxic MoA, although contribution weak cannot ruled out. Mechanistic support conclusions regarding hazard exposure weak. Comparison metabolism between humans provide little hazard. Three affected bioassays (forestomach, gland) present only brain anatomically different humans, diminishing relevance tumor these Extensive epidemiological not revealed causation cancer acrylonitrile.