Interactions of vinyl chloride with rat-liver DNA in vivo.

9beta-D-2'-Deoxyribofuranosyl-imidazo-[2,1-i]purine ("etheno-deoxyadenosine") and 1beta-D-2'-deoxyribofuranosyl-1,2-dihydro-2-oxo-imidazo-[1,2-c]pyrimidine ("etheno-deoxycytidine") are identified in the enzyme hydrolysates obtained (i) from calf-thymus DNA which had been modified by chemical reaction with chloroacetaldehyde and (ii) from liver DNA prepared from rats which had been exposed orally to vinyl chloride in their drinking water (250 ppm) for approx. 2 years. Thus, vinyl chloride-derived chloroethylene oxide and/or chloroacetaldehyde behaves as a bifunctional alkylating agent towards deoxyadenosine and deoxycytidine residues of DNA. The separation of deoxyribonucleosides and the two etheno-deoxyribosyl-nucleosides by liquid chromatography, and the mass spectra of etheno-deoxyadenosine and etheno-deoxycytidine and of their O-bis-(trimethylsilyl) derivatives are described. In the animal experiment (ii), the resulting proportion of etheno-deoxyadenosine is small compared with that of etheno-deoxycytidine. Imidazo-[2,1-i]purine (etheno-adenine) is identified: (a) in the supernatant after sedimentation of the modified DNA in the model experiment (i), and (b) in the product resulting from the reaction between chloroacetaldehyde and deoxyadenosine. The effect on the structure of DNA of the imidazo-cyclization of deoxyadenosine and deoxycytidine residues and of the depurination of etheno-deoxyadenosine residues is discussed in relation to vinyl chloride oncogenicity.