Sequential morphological and biological changes in the glandular stomach induced by oral administration of catechol to male F344 rats

Histogenesis and mechanisms of catechol-induced rat glandular stomach carci nogenesis were investigated in male F344 rats. Groups of 5 or 6 rats were t reated with dietary catechol at doses of 1, 0.5, 0.1, and 0.01% for 12 hr o r for 1, 2, 3, or 7 days or at a dose of 0.8% for 1, 2, 4, 12, and 24 wk; r ats were then euthanatized. The initial morphological changes were edema of the gastric wall, inflammatory-cell infiltration, erosion in the pyloric r egion close to the duodenum, and considerable increase in apoptosis at I:! hr; later, changes included augmented DNA synthesis and cell proliferation, as evaluated by bromodeoxyuridine labeling index and thickness of mucosa, respectively, on day 1. Downward hyperplasia due to excess regeneration app eared at edges of ulceration at week 2. This lesion disappeared, and then s ubmucosal hyperplasia appeared in the course of adenoma development. Only s light expression of c-myc or c-fos was apparent after 30-min oral administr ation or 1-, 3-, and 6-hr oral administration of catechol. No increase in l ipid peroxide levels was evident in gastric epithelium fed catechol for I w k. The amount of catechol distributed in the glandular stomach and forestom ach epithelium, which is not a target for carcinogenesis, did not differ I, 3, 6, and 24 hr after a single intragastric dose of 75 mg/kg body weight. Amounts of catechol bound to tissue protein were also not specifically high in the glandular stomach. These results indicate that regenerative cell pr oliferation due to toxicity plays an important role in catechol-induced gla ndular stomach carcinogenesis. Protein binding and free radicals may not be largely responsible for the toxicity.