Tyl Rochelle W, Friedman Marvin A
RTI, Center for Life Sciences and Toxicology, PO Box 12194, 3040 Cornwallis Road, Research Triangle Park, NC 27709-2194, USA.
Reprod Toxicol. 2003 Jan-Feb;17(1):1-13. doi: 10.1016/s0890-6238(02)00078-3.
Acrylamide monomer causes peripheral neurotoxicity, mutagenicity, clastogenicity, male reproductive toxicity, prenatal lethality, and endocrine-related tumors in rodents. Acrylamide (and/or its metabolite glycidamide) binds to dopamine receptors and spermatid protamines and inhibits activity of kinesin and dyneine, resulting in interference with neuronal intracellular transport and sperm motility. Glycidamide binds to various proteins and DNA. Acrylamide at low doses decreases litter size, with rats more sensitive than mice. At higher doses, sperm morphology and motility and neurotoxicity are affected, which decreases mating frequency. Acrylamide does not affect female reproduction (females exhibit neurotoxicity). Dominant lethal mutations cause decreased newborn litter size. The mechanisms of action appear to be: (1) acrylamide/glycidamide binding to spermatid protamines, causing dominant lethality and effects on sperm morphology; and (2) acrylamide binding to motor proteins, causing distal axonopathy, including hindlimb weakness/paresis, and effects on mounting, sperm motility, and intromission. Glycidamide-induced mutations appear to play no role in reproductive or neurologic toxicity.
丙烯酰胺单体可导致啮齿动物出现周围神经毒性、致突变性、染色体断裂性、雄性生殖毒性、产前致死性以及与内分泌相关的肿瘤。丙烯酰胺（和/或其代谢产物环氧丙酰胺）与多巴胺受体和精子细胞鱼精蛋白结合，并抑制驱动蛋白和动力蛋白的活性，从而干扰神经元细胞内运输和精子活力。环氧丙酰胺与多种蛋白质和DNA结合。低剂量的丙烯酰胺会使产仔数减少，大鼠比小鼠更敏感。在较高剂量下，精子形态、活力和神经毒性会受到影响，进而降低交配频率。丙烯酰胺不影响雌性生殖（雌性表现出神经毒性）。显性致死突变会导致新生仔畜数量减少。其作用机制似乎为：（1）丙烯酰胺/环氧丙酰胺与精子细胞鱼精蛋白结合，导致显性致死并影响精子形态；（2）丙烯酰胺与运动蛋白结合，导致远端轴索性神经病，包括后肢无力/轻瘫，并影响爬跨、精子活力和插入。环氧丙酰胺诱导的突变似乎在生殖或神经毒性中不起作用。
