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.
D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000494:pharmacology; D000241:Adenosine / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003596:Cytosine / Q000378:metabolism; D003854:Deoxyribonucleotides / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D011061:Poly A / Q000378:metabolism; D011066:Poly C / Q000378:metabolism; D012265:Ribonucleotides / Q000378:metabolism*; D013696:Temperature
D003854:Deoxyribonucleotides; D012265:Ribonucleotides; D011061:Poly A; C015465:poly(dA); C023826:poly(dC); D011066:Poly C; D003596:Cytosine; C004656:chloroacetaldehyde; D000079:Acetaldehyde; D000241:Adenosine