苯与甲醛对小鼠胚胎的联合毒性效应研究

Combined Toxicity of Benzene and Formaldehyde on Mouse Embryos in Vitro

背景与目的:观察苯和甲醛对胚胎发育的联合毒性作用,并探讨联合作用类型。材料与方法:采用体外全胚胎培养模型,按照3×4析因设计的要求共分12组。将8.5日龄昆明种小鼠胚胎与含不同浓度苯和甲醛的即刻离心血清共培养48 h,观察苯和甲醛对小鼠胚胎生长发育和组织器官形态分化的影响及其对胚胎卵黄囊结构的损伤作用,并通过直观分析和方差分析判断苯与甲醛联合作用的类型。结果:空白和溶剂对照组培养胚胎与体内同龄胚胎的发育基本一致(P>0.05);苯和甲醛对小鼠胚胎发育均具有抑制作用,生长发育和器官分化各指标均低于对照组(P<0.01),且呈剂量-效应关系,较高浓度时可诱发胚胎畸型,甚至死亡,其主要表现为头部异常、心脏发育异常、肢芽小、眼、耳、鳃弓和体位异常等;胚胎卵黄囊细胞结构紊乱、排列不规则,变性、肿胀,胞浆出现空泡。苯与甲醛对胚胎的毒作用表现为协同效应。结论:苯和甲醛对小鼠胚胎具有直接的胚胎发育毒性和致畸性,二者表现为协同毒性效应。

BACKGROUND AND AIM： To explore the combined toxic effects of benzene and formaldehyde on mouse embryos in vitro. MATERIALS AND METHODS： Whole embryo culture system was adopted. According to 3 x 4 factorial design, 12 groups were set up. The 8.5-day isolated mouse embryos were cocultured for 48 hours in freshly centrifuged serum with different concentrations of benzene and formaldehyde. The growth, development and morphodifferentiation of tissues and organs of mouse embryos were studied. The type of combined toxic effects of benzene and formaldehyde was analyzed by ANOVA and direct-viewing analysis. RESULTS： There were no statistically significant differences in embryonic growth and development among control groups in vitro and in vivo group （P 〉 0.05） . Benzene and formaldehyde had obvious toxic effect on growth and development in embryos in a dose-dependent manner every index of growth and development, morphodifferentiantion of tissues and organs demonstrated significant differences compared with the solvent control （P 〈 0.05） . With the increasing concentrations of benzene and formaldehyde, the incidence of malformation and death of embryo increased. Structure, arrangement and cell polarity of VYS endodermis ceils were influenced. When benzene was combined with formaldehyde, the severity of the toxic effects on the embryo was stronger than the addition of the two agents alone. CONCLUSION： Benzene and formaldehyde could cause synergistic developmental toxicity and teratogenicity to embryo in vitro.