Bedell M A, Dyroff M C, Doerjer G, Swenberg J A
IARC Sci Publ. 1986(70):425-36.
Etheno adducts can be formed by the reaction of vinyl chloride metabolites with DNA and may play a role in the carcinogenicity of this chemical. These adducts are highly fluorescent and may be quantitated by sensitive photometric methods in conjunction with high-performance liquid chromatographic (HPLC) separation. Three HPLC systems were evaluated on the basis of maximal fluorescence intensity and resolution of two etheno adducts, ethenodeoxycytidine and ethenodeoxyadenosine. Analyses were conducted with enzymatically digested DNA that had been incubated with chloroacetaldehyde, a vinyl chloride metabolite which may cause etheno adduct formation in vivo. All three known etheno adducts of DNA were tentatively identified in DNA reacted in vitro. The sensitivity of the method was highest for the ethenodeoxyadenosine adduct, with the limit of detection (1 pmol per injection in the HPLC system) being similar to that for O6-methylguanine, another promutagenic DNA adduct for which quantitation by HPLC with fluorescence detection has been reported. The method described here may be useful for the analysis of DNA from animals or humans exposed to vinyl chloride.
氯乙烯代谢产物与DNA反应可形成乙烯基加合物，其可能在该化学物质的致癌性中发挥作用。这些加合物具有高度荧光性，可通过灵敏的光度法结合高效液相色谱（HPLC）分离进行定量分析。基于两种乙烯基加合物（乙烯基脱氧胞苷和乙烯基脱氧腺苷）的最大荧光强度和分离度，对三种HPLC系统进行了评估。分析使用的是经酶消化的DNA，该DNA已与氯乙醛一起孵育，氯乙醛是一种氯乙烯代谢产物，可能在体内导致乙烯基加合物的形成。在体外反应的DNA中初步鉴定出了所有三种已知的DNA乙烯基加合物。该方法对乙烯基脱氧腺苷加合物的灵敏度最高，检测限（在HPLC系统中每次进样1皮摩尔）与O6-甲基鸟嘌呤相似，O6-甲基鸟嘌呤是另一种已报道可通过HPLC荧光检测进行定量的促突变DNA加合物。本文所述方法可能有助于分析接触氯乙烯的动物或人类的DNA。
