J. Whysner et al., EVALUATION OF POSSIBLE GENOTOXIC MECHANISMS FOR ACRYLONITRILE TUMORIGENICITY, Regulatory toxicology and pharmacology, 27(3), 1998, pp. 217-239
Acrylonitrile (ACN) exposure is associated with tumors in rat brain, Z
ymbal gland, and mammary gland. Adducts affecting base pairing were fo
rmed in isolated DNA exposed in vitro to the ACN metabolite cyano-ethy
lene oxide (CNEO). DNA from liver, which is not a cancer target organ
in ACN-exposed rats, contained low levels of 7-(2-oxoethyl)guanine, an
adduct believed not to interfere with base pairing. No adducts have b
een detected in brain DNA from ACN-exposed rats, suggesting that brain
tumors may have arisen by mechanisms other than ACN-DNA reactivity. G
enotoxicity assays of ACN have indicated no particular carcinogenic me
chanism. Positive reverse mutagenesis in Salmonella typhimurium HisG46
base substitution tester strains by ACN is attributable to CNEO. Othe
r in vitro genotoxicity test assays of ACN have yielded mixed results,
without consistent effect of metabolic activation. Some positive geno
toxicity data for ACN appear to result from artifacts or from non-DNA-
reactive mechanisms. lit vivo micronucleus, chromosome aberration, and
autoradiographic unscheduled DNA synthesis assays were negative for A
CN. The comparative genotoxicity of vinyl chloride and ACN indicates t
hat despite other similarities, they cause rodent tumors by different
mechanisms. Also, the absence of ACN-DNA adduct formation in the rat b
rain suggests the operation of epigenetic mechanisms. (C) 1998 Academi
c Press.