Sega G A, Alcota R P, Tancongco C P, Brimer P A
Biology Division, Oak Ridge National Laboratory, TN 37831-8077.
Mutat Res. 1989 Aug;216(4):221-30. doi: 10.1016/0165-1161(89)90008-3.
Mice received an intraperitoneal injection of 14C-labeled acrylamide (AA) at an exposure of 125 mg/kg to equal that used in genetic studies carried out by Shelby et al. (1986). Subsequently, spermatozoa were recovered from the reproductive tracts of the animals over a 3-week period and assayed for the amount of bound AA. A strong increase in the level of binding occurred in late-spermatid to early-spermatozoa stages; these same stages are also genetically most sensitive to the action of AA. At all time points, alkylation of DNA within the sperm accounted for a very small fraction (generally less than 0.5%) of the total sperm-head alkylation. However, alkylation of protamine, a protein unique to sperm cells, was found to be correlated with total sperm-head alkylation and accounted for essentially all of the AA binding. Two radioactive adducts were found in hydrolysed protamine samples, one of which co-eluted with a standard of S-carboxyethylcysteine. Protamine alkylation appears to be a significant cause of acrylamide-induced genetic damage in spermiogenic cells of the mouse.
小鼠腹腔注射14C标记的丙烯酰胺(AA),剂量为125mg/kg,与Shelby等人(1986年)进行的遗传学研究中使用的剂量相同。随后,在3周的时间内从动物生殖道中回收精子,并检测结合的AA量。在精子细胞后期到早期精子阶段,结合水平显著增加;这些相同阶段在遗传上对AA的作用也最为敏感。在所有时间点,精子内DNA的烷基化仅占精子头部总烷基化的极小部分(通常小于0.5%)。然而,发现精蛋白(一种精子细胞特有的蛋白质)的烷基化与精子头部总烷基化相关,并且基本上占了所有AA的结合。在水解的精蛋白样品中发现了两种放射性加合物,其中一种与S-羧乙基半胱氨酸标准品共洗脱。精蛋白烷基化似乎是丙烯酰胺诱导小鼠生精细胞遗传损伤的一个重要原因。