Lack of correlation between alkaline DNA fragmentation and DNA covalent binding induced by polychloroethanes after in vivo administration. Problems related to the assessment of a carcinogenic hazard

Abstract

The DNA-damaging activity of polychloroethanes was tested in mouse liver by the fluorometric assay of DNA unwinding. With the exception of 1,2-dichloroethane, all components of this chemical class had negative results. The failure of the parameter alkaline "DNA fragmentation" to detect the DNA-damaging activity of polychloroethanes is in sharp contrast with the measurement of DNA covalent binding, another short-term parameter of genotoxicity. Since covalent DNA adducts appear to be quantitatively well correlated with the oncogenic potencies of chloroethanes in liver, the negative results obtained with the present method can perhaps be explained in terms of quality of DNA adducts; these may be incapable of producing DNA breaks or alkali-labile sites detectable as alkaline DNA fragmentation. It is however worth noting that carcinogenicity of chloroethanes appears to depend not only on DNA damaging capability, but also on promoting activity during the carcinogenic process.