噻二唑类化合物的致畸作用初步研究

噻二唑类化合物具有抗肿瘤作用或对水稻白叶枯病、水稻细菌性条斑病、花生青枯病和柑桔溃疡病有良好的防治效果。本文对噻二唑类化合物不同剂型的致畸性和不同种属在致畸反应上的差异以及它们的致畸和解毒机理,进行了初步探讨。根据我们的实验,可以认为Bis-ATDA、A-TDA和Bis-HM-A-TDA均是较强的致畸原,致畸机理都是由于取代了辅酶Ⅰ(COI)中的烟酰胺而造成辅酶Ⅰ的合成和利用失调,最终影响了DNA和RNA的合成,导致胚胎细胞死亡之故。

PRELIMINARY STUDY ON THE TERATOGENIC EFFECT OF THIADIAZOLE COMPOUNDS

The present experiment was conducted with sexually mature, virgin female rats and mice. The females and males were mated over-night, then the pregnant rats and mice were divided into groups (see tables 1～8). All compounds were given orally on day 10 of gestation.The rats were killed on day-20 of gestation so as to count the number of corpora lutea, implantation sites and live fetuses. The female mice were killed on the day of parturition. The number of implantation, resorption sites and living fetuses were also counted. The living fetuses of the rats and mice were removed, weighted, inspected for gross abnormalities and sexes.Under our experimental conditions, the following results were obtained:Three thiadiazole compounds of Bis-A-TDA, A-TDA, and Bis-HM-A-TDA produced significant teratogenic effects on pregnant rats and mice. The teratogenic activity was as follows: Bis-A-TDA>A-TDA>Bis-HM-A-TDAThere is a significant species difference in embryo-toxicity and feto-toxicity of Bis-A-TDA, that is, rats are more susceptible than mice.For rats, suspension of Bis-A-TDA is more toxic than the boiled solution, probably as a result of partial conversion of Bis-A-TDA to A-TDA on boiling.