Relationship between the time of sustained ethyl acrylate forestomach hyperplasia and carcinogenicity

Chronic administration of ethyl acrylate (EA) by gavage at 100 or 200 mg/kg/day resulted in a significant dose-dependent increase in the incidence of forestomach (FS) squamous cell papillomas and carcinomas in both sexes of F344 rats and B6C3F1 mice. Subsequent work in this laboratory was designed to investigate the relationship between EA-induced FS hyperplasia and carcinogenicity. Current studies have focused on determining the time required for sustained FS hyperplasia to produce neoplastic transformation. Results of these studies demonstrated that gavage administration of EA to male F344 rats at 200 mg/kg/day for 6 or 12 months caused a sustained increase in FS epithelial hyperplasia for as long as exposure to EA continued. However, FS hyperplasia regressed, and no neoplasms developed when animals receiving EA for 6 months were allowed to recover until they were sacrificed at 24 months of age. In contrast, rats treated for 12 months and allowed 9 months recovery developed FS squamous cell carcinomas (3/13) and papillomas (1/13) for a combined incidence of 4/13. No gross lesions were detected in the liver of any of the rats treated with EA or corn oil vehicle, confirming the tissue specificity in the relationship between EA-induced FS hyperplasia and carcinogenesis. In conclusion, the present work has demonstrated that FS hyperplasia is selectively sustained at the site of EA-induced carcinogenicity for as long as EA is administered and has also demonstrated a temporal relationship between FS mucosal hyperplasia and the development of FS neoplasia by EA.(ABSTRACT TRUNCATED AT 250 WORDS)