灭幼脲光解产物DNA加合物的研究

INVESTIGATION OF DNA-2-CHLORO-BENZAMIDE ADDUCT

灭幼脲(邻氯苯甲酰基-对氯苯基-脲)本身是一种低毒、低残留、没有致突、致癌性的农药.但是它的某些分解产物,如:氯苯、对氯苯、对氯苯基脲等有一定的毒性.邻氯苯甲酰胺(灭幼脲的主要光解产物——CBA)和未经分离的灭幼脲光解产物的混合物,在试管反应条件下能与小牛胸腺DNA反应形成多种DNA加合物,用P_1加强灵敏度的^(32)P后标记方法分析,有四种DNA加合物被检出(DNA-CBA),实验证明,邻氯苯甲酸胺和灭幼脲光解产物的混合物在Ames实验中也均呈阳性结果,初步说明两者都可能具有一定的致突性.经单独碱基和邻氯苯甲酰胺试管反应的加合物鉴定,验证出其中较强的一种加合物是邻氯苯甲酸酰与2’-脱氧腺嘌吟-3’-单磷酸碱基(dAMP)反应所形成的加合物(dA-CBA),已占所形成加合物总量的57%.从^(32)P后标记方法所测的DNA加合物的自显影指纹图上可以看出,邻氯苯甲酰胺和灭幼脲光解产物混合物的DNA加合物具有相同的迁移特性.初步说明,尽管灭幼脲原体化合物没有致突性,但它的主要光解产物邻氯苯甲酰胺具有一定基因突变性,所以不仅应对原体化合物进行评价,而且还必须对它的分解物和代谢物同时进行安全评价.

In vitro reaction of DNA with 2-chlorobenzamide which is photoproduct of 2-chloro-N ( ( (4-chlorophenyl)amino)carbonyl)benzamide produced four DNA adducts,as determined by 32P-postlabeling. When 2-chlorobenzamide was reacted in vitro with deoxyri-bonucleotedes-3'-monophosphate,two adducts were observed from 2'-deoxyadenosine-3-monophosphate, none from other three 2'-deoxyribonucleotades-3-monophosphate. Chromatographic comparison of the adducts formed in DNA with those formed with the deoxyribonucleotedes suggests that deoxyadenosion is the primary site of DNA modification. RAL of DNA-2'chlorobenzamide adducts was (1.0-254.9) ×10-9.