Toxicity, DNA Binding, and Cell Proliferation in Male F344 Rats following Short-term Gavage Exposures to Trans-2-Hexenal

Hexenal is a genotoxic compound to which humans are exposed daily through the consumption of foods and beverages. The present studies were conducted to examine the relationships between the dose-responses of trans-2-hexenal-induced toxicity, DNA adduct formation, and cell proliferation. Male F344 rats were exposed by gavage to single doses of up to 500 mg/kg and killed 1, 2, or 4 days after dosing or were exposed to repeat doses of up to 100 mg/kg once daily for 5 days or 5 days per week for 4 weeks and killed 1 day after the end of the dosing period. Histologically, the primary observations were necroulcerative lesions, inflammation, and hyperplasia in the forestomach and inflammation in the glandular stomach. Hexenal-derived DNA adduct formation and cell proliferation were induced in the forestomach at doses of hexenal that also induced gastric toxicity; DNA adducts were not observed in the glandular stomach. These findings suggest that the toxicity of hexenal was limited to the site of contact (stomach...