Abstract
Acrylonitrile (CH2 = CH-CN), a plastic monomer, is known to produce microglioma of the central nervous system, cell papillomas of the stomach and squamous cell carcinoma. The molecular interaction of [2,314C]-acrylonitrile (VCN), its metabolites or both with proteins, RNA and DNA of various rat tissues after a single oral dose of 46.5 mg/kg has been studied. RNA and DNA molecules were separated by hydroxyapatite chromatography, and the DNA nucleosides were separated after enzymic hydrolysis by high performance liquid chromatography (HPLC). Binding of VCN to proteins of various tissues was extensive and time dependent. Radioactivity incorporated in the nucleic acids was highest in liver and the target organs stomach and brain. DNA alkylation, which increased by time, was significantly higher in the target organs, brain and stomach (119 and 81 pmol/mg respectively) than that in the liver (25 pmol/mg). The covalent binding indices for liver, stomach and brain were 6, 52, and 65 respectively. HPLC analysis of DNA hydrolysate revealed that by 24 h most of the applied radioactivity appeared in peaks corresponding to standard deoxyguanosine and deoxyadenosine. These results are consistent with the ability of VCN to act as a multipotent carcinogen by preferential alkylation of DNA in the extrahepatic target tissues, stomach and brain.Key wordsCarcinogenicityMolecular interactionDNA bindingCovalent bindingEnvironmental toxicology
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