Hyperkeratinization and hyperplasia of the forestomach epithelium in vitamin A deficient rats

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Abstract
Specific pathogen free F-344 rats were kept on a vitamin A deficient diet for 3–5 months. After 3 months on this diet the forestomach epithelium showed a mild atrophy. Stereological cytology showed a marked increase in the volume density of cytoplasmic filament bundles and decrease in the volume density of non-bundled cytoplasmic filaments. The volume fraction of keratohyalin granules increased whereas the volume fraction of membrane coating granules decreased. Some animals maintained for 4–5 months on the hypovitaminic diet exhibited the same mild atrophic forestomach epithelium accompanied by hyperkeratinization. Others showed a marked epithelial atrophy and 4 out of 12 animals revealed a marked hyperplasia with increased3H thymidine labeling index and several papillomatous proliferations. Although many of these alterations reflect a decrease in proliferation as well as hyperkeratinization, the latter changes were not unlike those produced by known carcinogens, and support the putative important role of vitamin A in both carcinogenesis and chemoprevention.