Chemically-induced neoplasia is a major public health concern and is the driving force behind much of the research conducted by the NTP. Present work has focused on mechanisms of chemically-induced forestomach carcinogenesis. One area of interest has been the relationship between chemical-induced early cell proliferation and carcinogenicity. Ethyl acrylate (EA) was selected as a model chemical for these studies because chronic gavage administration of EA resulted in a dose- and concentration- dependent increase in the incidence of forestomach (FS) neoplastic lesions in both sexes of F344 rats and B6C3F1 mice. No neoplastic lesions were found at any other site. The current work investigated the correlation between the induction of cell proliferation in the male rat FS (target) and liver (nontarget) and the carcinogenicity of EA. Cell proliferation was measured by assessing bromodeoxyuridine (BrDU) incorporation into DNA administered by osmotic minipump concurrent with gavage treatment with EA (50, 100 or 200 mg/kg/day) for 2, 4, or 8 days. BrDU incorporation was detected immunohistochemically. Results of these studies indicated that EA induced epithelial cell proliferation in the FS was dose- and time- dependent. Minimal or no cell proliferation was detected in the livers of EA-treated rats. These results suggest a positive correlation between cell proliferation in the target tissue and carcinogenicity.
