In vivo and in vitro binding of epichlorohydrin to nucleic acids

Epichlorohydrin (EC) binds to macromolecules of biological relevance in vivo: DNA is less labelled than RNA and proteins, rat organs interact more than mouse organs, stomach is the most labelled organ with liver, kidney and lung involved in decreasing order. Based on the Covalent Binding Index (CBI), EC is a weak-moderate oncogen, just as other chlorinated hydrocarbons such as 1,2-dichloroethane and carbon tetrachloride. An interaction of EC with nucleic acids (DNA and polyribonucleotides) occurs also in vitro. It is mediated either by chemical reactivity per se of the molecule (near-UV (NUV) irradiation does not photoactivate EC) and by enzymatic (microsomal and/or cytosolic) fractions, whose relative effectiveness is variable in relation to the organ tested. The best substrates for interaction are poly(G) and poly(A) when using microsomal and cytosolic fractions, respectively, whereas the labelling of double-stranded DNA is always lower. On the whole, the picture of enzyme (microsome + cytosol)-mediated in vitro interaction is similar to the pattern of in vivo binding, with the exception of rat stomach enzymes which are inactive in vitro.