The effect of oxygen concentration on the teratogenicity of salicylate, niridazole, cyclophosphamide, and phosphoramide mustard in rat embryos in vitro.
The effect of oxygen concentration on the teratogenicity of salicylate, niridazole, cyclophosphamide, and phosphoramide mustard in rat embryos in vitro.
复制标题
氧浓度对水杨酸盐、硝达唑、环磷酰胺和磷酰胺芥子气在体外大鼠胚胎致畸性的影响。
DOI：
10.1002/tera.1420320217
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Fantel,AG
中科院分区：
文献类型：
--
作者：
Greenaway,JC;Mirkes,PE;Walker,EA;Juchau,MR;Shepard,TH;Fantel,AG
比较了在水杨酸盐（SAL）、环磷酰胺（CP）、硝哒唑（NDZ）或磷酰胺芥（PM）存在下，在5%或20%氧气条件下培养的大鼠胚胎。采用多元回归分析比较药物浓度、氧浓度和药物与氧浓度乘积对培养24 h胚胎畸形发生率、存活率和蛋白质含量的影响。药物浓度对畸形的发生率、严重程度和蛋白质含量均有显著影响（P < 0.001）。氧浓度对四种化合物的蛋白质含量有显著影响（P < 0.001），但仅对NDZ的畸形发生率有影响。此外，氧浓度和药物浓度的交互作用显著影响NDZ存在下的畸形发生率（P < 0.001），蛋白质含量（P < 0.001）和活力（P < 0.001）。自变量的显著影响模式（药物浓度、氧浓度和药物乘以氧浓度）与所讨论药物的氧依赖性代谢（或缺乏代谢）的假设一致。NDZ被认为是通过氧抑制的硝基还原酶转化为活性中间体，在氧张力降低时毒性更大。CP由氧依赖性P-450系统激活，随着氧张力的增加毒性更大。胚胎暴露于SAL或PM的显着影响的独立变量是一致的控制胚胎的影响，特别是，增加蛋白质含量与氧气的增加。
Comparisons were made of rat embryos cultured at 5% or 20% oxygen in the presence of salicylate (SAL), cyclophosphamide (CP), niridazole (NDZ), or phosphoramide mustard (PM). Multiple regression analyses were used to compare the effects of drug concentration, oxygen concentration, and the product of drug times oxygen concentration on malformation incidence, viability, and protein content of embryos cultured for 24 hours. Drug concentration significantly affected malformation incidence or severity and protein content (P < 0.001) for the four drugs tested. Oxygen concentration significantly affected protein content for the four compounds (P < 0.001) but affected malformation incidence only with NDZ. Furthermore, the interaction of oxygen concentration and drug concentration significantly affected the malformation incidence in the presence of NDZ (P < 0.001), and protein content (P < 0.001) and viability (P < 0.001) in the presence of CP.The pattern of significant effects of the independent variables (drug concentration, oxygen concentration, and drug times oxygen concentration) is consistent with the hypotheses of oxygen‐dependent metabolism (or lack of metabolism) of the drugs in question. NDZ, which is thought to be converted to reactive intermediates by an oxygen‐inhibited nitroreductase, was more toxic at reduced oxygen tension. CP, which is activated by an oxygen‐dependent P‐450 system, was more toxic with increased oxygen tension. Significant effects of the independent variables on embryos exposed to SAL or PM were consistent with the effects on control embryos, notably, increased protein content with increased oxygen.