Whysner J, Ross P M, Conaway C C, Verna L K, Williams G M
Toxicology and Risk Assessment Program, American Health Foundation, Valhalla, New York 10595, USA.
Regul Toxicol Pharmacol. 1998 Jun;27(3):217-39. doi: 10.1006/rtph.1998.1204.
Acrylonitrile (ACN) exposure is associated with tumors in rat brain, Zymbal gland, and mammary gland. Adducts affecting base pairing were formed in isolated DNA exposed in vitro to the ACN metabolite cyanoethylene oxide (CNEO). DNA from liver, which is not a cancer target organ in ACN-exposed rats, contained low levels of 7-(2-oxoethyl)guanine, and adduct believed not to interfere with base pairing. No adducts have been detected in brain DNA from ACN-exposed rats, suggesting that brain tumors may have arisen by mechanisms other than ACN-DNA reactivity. Genotoxicity assays of ACN have indicated no particular carcinogenic mechanism. Positive reverse mutagenesis in Salmonella typhimurium HisG46 base substitution tester strains by ACN is attributable to CNEO. Other in vitro genotoxicity test assays of ACN have yielded mixed results, without consistent effect of metabolic activation. Some positive genotoxicity data for ACN appear to result from artifacts or from non-DNA-reactive mechanisms. In vivo micronucleus, chromosome aberration, and autoradiographic unscheduled DNA synthesis assays were negative for ACN. The comparative genotoxicity of vinyl chloride and ACN indicates that despite other similarities, they cause rodent tumors by different mechanisms. Also, they absence of ACN-DNA adduct formation in the rat brain suggests the operation of epigenetic mechanisms.
接触丙烯腈（ACN）与大鼠脑、齐默尔氏腺和乳腺中的肿瘤有关。在体外暴露于ACN代谢物氰基环氧乙烷（CNEO）的分离DNA中形成了影响碱基配对的加合物。来自肝脏的DNA（肝脏在接触ACN的大鼠中不是癌症靶器官）含有低水平的7-（2-氧代乙基）鸟嘌呤，这种加合物被认为不会干扰碱基配对。在接触ACN的大鼠的脑DNA中未检测到加合物，这表明脑肿瘤可能是通过ACN与DNA反应性以外的机制产生的。ACN的遗传毒性试验未表明有特定的致癌机制。ACN在鼠伤寒沙门氏菌HisG46碱基取代测试菌株中引起的正向回复突变归因于CNEO。ACN的其他体外遗传毒性试验结果不一，代谢活化没有一致的影响。ACN的一些阳性遗传毒性数据似乎是由假象或非DNA反应机制导致的。ACN的体内微核、染色体畸变和放射自显影非预定DNA合成试验均为阴性。氯乙烯和ACN的比较遗传毒性表明，尽管它们有其他相似之处，但它们通过不同的机制导致啮齿动物肿瘤。此外，大鼠脑中不存在ACN-DNA加合物的形成表明存在表观遗传机制。
