Dearfield K L, Douglas G R, Ehling U H, Moore M M, Sega G A, Brusick D J
U.S. Environmental Protection Agency, Office of Pesticide Programs, Washington, DC 20460, USA.
Mutat Res. 1995 Aug;330(1-2):71-99. doi: 10.1016/0027-5107(95)00037-j.
An updated review of the genotoxicity studies with acrylamide is provided. Then, using data from the studies generating quantitative information concerning heritability of genetic effects, an assessment of the heritable genetic risk presented by acrylamide is presented. The review offers a discussion of the reactions and possible mechanisms of genotoxic action by acrylamide and its epoxide metabolite glycidamide. Several genetic risk approaches are discussed, including the parallelogram, direct (actually a modified direct), and doubling dose approaches. Using data from the specific-locus and heritable translocation assays, the modified direct and doubling dose approaches are utilized to quantitate genetic risk. Exposures of male parents to acrylamide via inhalation, ingestion, and dermal routes are also quantitated. With these approaches and measurements and their underlying assumptions concerning extrapolation factors (including germ cell stage specificity, DNA repair variability, locus specificity), number of human loci associated with dominant disease alleles, and spontaneous mutation rates, an assessment of heritable genetic risk for humans is calculated for the three exposure scenarios. The calculated estimates for offspring from fathers exposed to acrylamide via drinking water are up to three offspring potentially affected with induced genetic disease per 10(8) offspring. Estimates for inhalation or dermal exposures suggest higher risks for induced genetic disease in offspring from fathers exposed in occupational settings.
本文提供了对丙烯酰胺遗传毒性研究的最新综述。然后，利用来自产生有关遗传效应遗传性的定量信息的研究数据，对丙烯酰胺呈现的可遗传遗传风险进行了评估。该综述讨论了丙烯酰胺及其环氧化物代谢产物环氧丙酰胺的遗传毒性作用反应和可能机制。讨论了几种遗传风险评估方法，包括平行四边形法、直接法（实际上是改良直接法）和加倍剂量法。利用特定位点和可遗传易位试验的数据，采用改良直接法和加倍剂量法对遗传风险进行定量。还对雄性亲本通过吸入、摄入和皮肤途径接触丙烯酰胺的情况进行了定量。通过这些方法、测量及其关于外推因子（包括生殖细胞阶段特异性、DNA修复变异性、位点特异性）、与显性疾病等位基因相关的人类基因座数量以及自发突变率的基本假设，针对三种暴露情况计算了对人类的可遗传遗传风险评估。通过饮用水接触丙烯酰胺的父亲的后代的计算估计值为每10⁸个后代中多达三个可能受到诱发遗传疾病影响的后代。吸入或皮肤接触的估计值表明，职业环境中接触丙烯酰胺的父亲的后代患诱发遗传疾病的风险更高。
