Chloroacetaldehyde-treated ribo- and deoxyribopolynucleotides. 1. Reaction products

The in vitro reaction of the vinyl chloride metabolite chloroacetaldehyde (CAA) with cytosine and adenine residues in ribo- and deoxyribopolynucleotides leads to the formation of the relatively stable hydrated etheno derivatives 3,N4-(N4-alpha-hydroxyethene)adenine (epsilon C . H2O) and 1,N6-(N6-alpha-hydroxyethene)cytosine (epsilon A . H2O). Under physiological conditions the hydrates are slowly converted to 3,N4-ethenocytosine (epsilon C) and 1,N6-ethenoadenine (epsilon A). The half-life at pH 7.25 of epsilon C . H2O in poly(rC) is 4.9 h at 50 degrees C and of epsilon A . H2O in poly(rA) is 1.4 h at 37 degrees C. These dehydration rates in polymers are similar to those for hydrates in monomers. The reactivity of A and C residues is greatly suppressed in double-stranded polymers. Adenine residues are about 10 times less reactive in poly(rA) . poly(rU) than A in single-stranded polymers. Under similar reaction conditions no reaction of C residues in poly(rC) . poly(rG) was detected. In vinyl chloride exposed cells, where CAA is formed, the cyclic etheno derivatives of A and C are likely to occur preferentially in single-stranded regions of nucleic acids, with the hydrate forming a major proportion of the modification.