Blazak W F, Meier J R, Stewart B E, Blachman D C, Deahl J T
Cellular and Genetic Toxicology Department, SRI International, Menlo Park, CA 94025.
Mutat Res. 1988 Dec;206(4):431-8. doi: 10.1016/0165-1218(88)90050-x.
1,1,1- and 1,1,3-trichloroacetones (TCA) result from the disinfection of municipal water supplies with chlorine, and are direct-acting mutagens in the Ames/Salmonella assay. The objective of this study was to further investigate the genotoxicity of these compounds in mammalian cells using an in vitro chromosomal aberration assay in Chinese hamster ovary (CHO) cells and the micronucleus and spermhead abnormality assays in mice. Both compounds induced significant increases in structural chromosomal aberrations in CHO cells in the presence and in the absence of rat S9 metabolic activation (MA). 1,1,3-TCA was more cytotoxic to CHO cells but 1,1,1-TCA resulted in a higher proportion of cells with aberrations. The clastogenic activities of both compounds were reduced in assays conducted with MA. Neither compound resulted in the induction of a significant increase in micronucleated polychromatic erythrocytes from bone marrow of Swiss-Webster mice when administered by oral gavage; nor were effects seen on the incidence of sperm with head-shape abnormalities, testis weight, or epididymal sperm concentration in B6C3F1 mice 21 or 35 days after treatment. These data indicate that the drinking water contaminants 1,1,1- and 1,1,3-TCA are clastogenic in vitro, but are not clastogenic to bone marrow cells in vivo, and do not adversely affect several indicators of testicular function in mice.
1,1,1-三氯丙酮和1,1,3-三氯丙酮(TCA)是城市供水用氯消毒的产物,在艾姆斯/沙门氏菌试验中是直接作用的诱变剂。本研究的目的是使用中国仓鼠卵巢(CHO)细胞的体外染色体畸变试验以及小鼠的微核和精子头部异常试验,进一步研究这些化合物在哺乳动物细胞中的遗传毒性。在有和没有大鼠S9代谢活化(MA)的情况下,这两种化合物均能显著增加CHO细胞中的结构染色体畸变。1,1,3-TCA对CHO细胞的细胞毒性更大,但1,1,1-TCA导致出现畸变的细胞比例更高。在有MA的试验中,这两种化合物的致断裂活性均降低。经口灌胃给予瑞士韦伯斯特小鼠时,这两种化合物均未导致其骨髓中微核多染红细胞显著增加;在B6C3F1小鼠治疗后21天或35天,也未观察到对精子头部形状异常的发生率、睾丸重量或附睾精子浓度有影响。这些数据表明,饮用水污染物1,1,1-三氯丙酮和1,1,3-三氯丙酮在体外具有致断裂作用,但在体内对骨髓细胞没有致断裂作用,并且对小鼠的几种睾丸功能指标没有不利影响。