Dietary retinoids are essential for skin papilloma formation induced by either the two-stage or the complete tumorigenesis model in female SENCAR mice

Our previous work has shown that dietary retinoic acid (RA) is necessary for skin tumor formation induced by the two-stage protocol with the initiator 7,12-dimethylbenz[a]anthracene (DMBA) and the promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA) (De Luca et al., Cancer Res., 36 (1976) 2334-2339). Here we report that retinoids are required for tumorigenesis by the two-stage as well as by the complete tumorigenesis protocol. Mice were treated with a single dose of DMBA (20 μg), followed by 20 applications of TPA (2 μg), or by 20 applications of DMBA (25 μg for 2 weeks and 51 μg thereafter). Regardless of the tumor induction protocol, tumor formation was inhibited by vitamin A-deficiency, while RA (3 μg/g of diet) or retinyl palmitate (RP, 6 μg/g) supplementation permitted the appearance of tumors. In addition, in comparison to the purified diets and regardless of their RA levels, the non-purified Purina chow diet enhanced tumor yield especially in the two-stage tumorigenesis protocol. This effect was less striking in mice with tumors induced by the complete tumorigenesis protocol. In summary, dietary retinoids are essential for skin tumor formation induced either by the two-stage or the complete tumorigenesis protocol.