Studies on the toxicity of some glycol ethers and alkoxyacetic acids in primary testicular cell cultures.
Studies on the toxicity of some glycol ethers and alkoxyacetic acids in primary testicular cell cultures.
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一些乙二醇醚和烷氧基乙酸在原代睾丸细胞培养物中的毒性研究。
DOI：
10.1016/0041-008x(85)90146-2
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发表时间：
1985
影响因子：
3.8
通讯作者：
S. Gangolli
中科院分区：
文献类型：
--
作者：
T. Gray;E. Moss;D. Creasy;S. Gangolli
从未成熟大鼠的睾丸中制备支持细胞和生殖细胞的原代混合培养物，并研究了它们对已知睾丸毒物乙二醇单甲醚（EGM）和乙二醇单乙醚（EGE）的反应。当以高达 50 mm 的深度添加到培养基中 72 小时时，EGM 和 EGE 均未产生任何形态学毒性证据。相反，它们的代谢物甲氧基乙酸（MAA）和乙氧基乙酸（EAA）在2至10毫米下持续24至72小时会导致粗线期和分裂精母细胞（体内母醚的靶细胞）变性。与体内一样，早期的精母细胞、精原细胞和支持细胞似乎不受影响。 EAA 的效力低于 MAA，而正丙氧基乙酸和正丁氧基乙酸以及甲氧基乙酰甘氨酸（MAA 的进一步代谢物）在这些条件下不产生形态变化。在对大鼠进行的四种酸的同时研究中观察到了相同顺序的毒性。在培养物中，形态变化的严重程度与附着的生殖细胞部分中肉毒碱乙酰转移酶和乳酸脱氢酶-X活性的降低相平行。培养基分析没有提供 EGM 转化为 MAA 或其他代谢物或 MAA 进一步代谢的证据。烷氧基乙酸在培养物和体内的睾丸毒性之间的密切对应表明在这两种情况下具有相似的作用模式，并指出这些培养物对于机制研究和筛选目的的潜在价值。结果还强调了代谢在乙二醇醚睾丸毒性中的作用，并表明 MAA 是 EGM 的活性代谢物。
Primary mixed cultures of Sertoli and germ cells were prepared from testes of immature rats and their response to the known testicular toxicants ethylene glycol monomethyl ether (EGM) and ethylene glycol monoethyl ether (EGE) was studied. Neither EGM nor EGE produced any morphological evidence of toxicity when added to the culture medium at up to 50 mm for 72 hr. In contrast, their metabolites methoxyacetic acid (MAA) and ethoxyacetic acid (EAA) at 2 to 10 mm for 24 to 72 hr caused degeneration of the pachytene and dividing spermatocytes, the target cells of the parent ethers in vivo. As in vivo, earlier spermatocytes, spermatogonia, and Sertoli cells appeared unaffected. EAA was less potent than MAA whereas n-propoxy- and n-butoxyacetic acid, and methoxyacetylglycine, a further metabolite of MAA, produced no morphological changes under these conditions. The same order of toxicity was observed in concurrent studies with the four acids in rats. In culture, the severity of the morphological changes was paralleled by decreases in the activity of carnitine acetyltransferase and lactate dehydrogenase-X in the attached germ cell fraction. Analysis of culture medium provided no evidence for the conversion of EGM to MAA or other metabolites or for the further metabolism of MAA. The close correspondence between the testicular toxicity of alkoxyacetic acids in culture and in vivo suggests a similar mode of action in both cases and points to the potential value of these cultures for mechanistic studies and for screening purposes. The results also emphasize the role of metabolism in the testicular toxicity of glycol ethers and indicate that MAA in an active metabolite of EGM.