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维生素A同系物的体外发育毒性差异

In vitro differential developmental toxicity of vitamin A congeners.

作者信息

Johnson E M, Chun Y H

机构信息

Department of Anatomy, Jefferson Medical College, Philadelphia, Pennsylvania.

出版信息

Teratology. 1989 Apr;39(4):349-61. doi: 10.1002/tera.1420390407.

DOI:10.1002/tera.1420390407
PMID:2749578
Abstract

Several forms of vitamin A were tested in the in vitro hydra assay for their developmental toxicity hazard potential and site of action on progressive ontogenesis. Retinol, retinyl acetate, retinaldehyde, all trans retinoic acid, and 13 cis retinoic acid were tested fully, and each was established clearly as being able to perturb development of artificial hydra "embryos" at, or near, adult toxic treatment levels. All forms of vitamin A tested interfered with differentiation, but, although the alcohol, acetate, and aldehyde forms (group I) prevented the initial stages of differentiation from occurring, the acid forms (group II) allowed the initial stages of differentiation to occur but not the final differentiation of tentacle buds. Group I compounds produced the developmental toxicity endpoint after as little as 24 h of transient exposure on the first day of development, but had no permanent effect on development at their minimal affective developmental concentration (D-MAC) when exposure began after the first day of development. In contrast, transient 24-h exposure to group II forms did not interfere with development. At, or even above, a concentration greater than the D-MAC, more continuous exposure to them was required to interfere with differentiation. Consistent with tests of other chemicals, the concentrations needed to produce effects in hydra bore no relation to those needed to produce effects in mammals.

摘要

在体外水螅试验中,对几种形式的维生素A进行了测试,以评估它们对发育毒性的潜在危害以及对渐进性个体发育的作用部位。对视黄醇、乙酸视黄酯、视黄醛、全反式视黄酸和13-顺式视黄酸进行了全面测试,结果清楚地表明,在成年毒性治疗水平或接近该水平时,每种维生素A都能够干扰人工水螅“胚胎”的发育。所有测试的维生素A形式均干扰分化,但尽管醇、乙酸酯和醛形式(第一组)阻止了分化的初始阶段发生,酸形式(第二组)允许分化的初始阶段发生,但不允许触手芽的最终分化。第一组化合物在发育第一天短暂暴露仅24小时后就产生了发育毒性终点,但在发育第一天后开始暴露时,在其最小有效发育浓度(D-MAC)下对发育没有永久性影响。相比之下,短暂暴露24小时于第二组形式不会干扰发育。在等于或甚至高于D-MAC的浓度下,需要更多持续暴露于它们才能干扰分化。与其他化学物质的测试一致,在水螅中产生效应所需的浓度与在哺乳动物中产生效应所需的浓度无关。

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