Retinoid action on gene expression induced by low-LET irradiation of rat skin

Low LET (linear energy transfer) radiation is a potent inducer of skin cancer in the rat model. Retinoids have chemopreventive activity in several animal models including irradiated rat skin. As an initial effort to understand molecular mechanisms that lie behind the retinoid inhibition of radiation-induced cancer, this thesis work has demonstrated how a non-toxic, naturally occurring retinoid in the diet (retinyl acetate, i.e. vitamin A acetate, VAA) alters gene expression upon exposure of rat skin to electron. The differential display method based on gene chip technology has been used to identify genes whose expression is altered by electron radiation or by VAA or by the combination of both, and also those radiation-altered gene expression that are reversed by the presence of VAA. Results show that the radiation and VAA individually altered epidermal proliferation and differentiation, cellular and nucleic acid metabolism, stress response and inflammation genes. Furthermore, VAA strongly inhibited radiation induced expression of (1) basal cell proliferation marker keratin 14, (2) an intracellular calcium-binding and inflammation-related protein MRP14, and (3) several transcripts of MHC class 11 family. These results suggest that inhibition of proliferation and inflammation may explain how VAA reversed radiation effects on rat skin in vivo .