Williams J, Foster P M
Central Toxicology Laboratory, Imperial Chemical Industries plc, Nr Macclesfield, Cheshire, United Kingdom.
Toxicol Appl Pharmacol. 1988 Jun 15;94(1):160-70. doi: 10.1016/0041-008x(88)90346-8.
Lactate and pyruvate are hormonally stimulated products of the Sertoli cell, which are essential for germ cell survival. The utility of measuring these products as indices of Sertoli cell function was examined using toxicants targeted to this cell type. Hence, 1,3-dinitrobenzene (1,3-DNB; 10(-6) - 10(-4) M), and mono-(2-ethylhexyl)phthalate (MEHP; 10(-8) - 10(-4) M) were tested in rat Sertoli cell cultures. Both compounds produced significant dose-related increases (maximally three- to fourfold) in lactate concentrations in the culture medium. Only 1,3-DNB produced significant dose-related increases (up to eight- to ninefold) in pyruvate concentrations. All increases occurred within 24 hr of exposure, with the earliest changes occurring within 1-2 hr. The specificity of the responses was examined by comparison with the nontoxic isomers, 1,2 and 1,4-DNB, and the parent compound of MEHP, di-(2-ethylhexyl) phthalate and its inactive metabolite, 2-ethylhexanol. None of these compounds showed significant effects on lactate or pyruvate production. The spermatocyte toxicant, ethylene glycol monomethyl ether (EGME), and its major metabolite, methoxyacetic acid (MAA), were also tested. EGME had no effect on lactate or pyruvate production, and MAA produced a decrease in lactate concentration only at the maximum dose employed (5 mM). These results show that dose-related increases in lactate production were only observed for the two Sertoli cell toxicants, and only for 1,3-DNB in the case of pyruvate production. Inactive isomers, metabolites, and germ cell toxicants did not produce these changes. Thus, lactate (and pyruvate) production by rat Sertoli cell cultures may be a sensitive index of altered function as induced by 1,3-DNB and MEHP.
乳酸和丙酮酸是受激素刺激的支持细胞产物，对生殖细胞的存活至关重要。本研究使用针对该细胞类型的毒物，检测了将这些产物作为支持细胞功能指标进行测量的效用。因此，在大鼠支持细胞培养物中测试了1,3 - 二硝基苯（1,3 - DNB；10⁻⁶ - 10⁻⁴ M）和邻苯二甲酸单（2 - 乙基己基）酯（MEHP；10⁻⁸ - 10⁻⁴ M）。两种化合物均使培养基中乳酸浓度产生显著的剂量相关增加（最大增至三至四倍）。只有1,3 - DNB使丙酮酸浓度产生显著的剂量相关增加（增至八至九倍）。所有增加均在暴露后24小时内出现，最早的变化在1 - 2小时内发生。通过与无毒异构体1,2 - DNB和1,4 - DNB以及MEHP的母体化合物邻苯二甲酸二（2 - 乙基己基）酯及其无活性代谢物2 - 乙基己醇进行比较，检测了反应的特异性。这些化合物均未对乳酸或丙酮酸的产生显示出显著影响。还测试了精子细胞毒物乙二醇单甲醚（EGME）及其主要代谢物甲氧基乙酸（MAA）。EGME对乳酸或丙酮酸的产生没有影响，MAA仅在所用最大剂量（5 mM）时使乳酸浓度降低。这些结果表明，仅在两种支持细胞毒物作用下观察到乳酸产生的剂量相关增加，就丙酮酸产生而言，仅在1,3 - DNB作用下出现。无活性异构体、代谢物和生殖细胞毒物未产生这些变化。因此，大鼠支持细胞培养物中乳酸（和丙酮酸）的产生可能是1,3 - DNB和MEHP诱导的功能改变的敏感指标。
