MOLECULAR INTERACTION OF [2,3-C-14] ACRYLONITRILE WITH DNA IN GASTRICTISSUE OF RAT

Acrylonitrile (VCN) is used extensively in polymer industries, and is known to induce gastric cancer following oral administration. A paucit y of information exists regarding the mechanism(s) by which acrylonitr ile induces gastric neoplasia. The time course for uptake of radioacti vity by gastric tissue and covalent binding of [2,3-C-14] VCN or its m etabolites to gastric DNA were determined following a single oral dose of 46.5 mg/kg. The rates of DNA synthesis and repair, as measured by unscheduled DNA synthesis in the gastric tissue of VCN-treated rats, w ere also studied. Maximum tissue uptake and covalent binding of radioa ctivity to gastric DNA were observed at 15 minutes following [2,3-C-14 ] VCN administration. At 6 hours following VCN administration, signifi cant inhibition (37% of control) in gastric replicative DNA synthesis was observed. A rebound followed by an increase (211% of control) in r eplicative DNA synthesis was observed at 24 hours. A three-fold elevat ion in unscheduled DNA synthesis was observed at 24 hours following tr eatment with VCN. These results indicate that VCN or its metabolites i rreversibly interact with gastric DNA, causing DNA damage. The results also indicate that the delayed VCN-induced DNA repair, determined as unscheduled DNA synthesis, is inefficient for the removal of the resul ting DNA lesions.