Phytol is a novel tumor promoter on ICR mouse skin

Phytol is a branched, long-chain aliphatic alcohol which has various biolog ical effects. In this study, we examined phytol as a tumor promoter in a mo use skin initiation-promotion model, and compared its promotion activity wi th that of 12-O-tetradecanoyl phorbol-13-acetate (TPA). Female ICR mice, 7 weeks of age, were initiated with 100 mu g of 7,12-dimethylbenz(a)anthracen e, and were then topically promoted twice a week for 16 weeks with 100 mg o f phytol or with 2.5 mu g of TPA. In this model 95% of animals treated with phytol developed skin tumors within 16 weeks. The average number of lesion s per mouse treated with phytol was significantly lower than that in mice t reated with TPA, and this significant difference continued up to 16 weeks a fter the end of promotion treatment. Characterization of hyperplasia 48 h a fter topical application of agents showed that epidermal thickness and vert ical thickness following topical application of phytol were significantly i ncreased compared with vehicle controls, but were significantly smaller tha n in animals treated with TPA. Ornithine decarboxylase (ODC) activity follo wing topical application of phytol was increased in a dose-dependent manner and showed a weak, delayed induction (which was maximal 11-12 h after trea tment) as compared with the case of TPA. The specific binding of [H-3]phorb ol-12,13-dibutyrate (PDBU) by JB6 cells was not inhibited by phytol at conc entrations up to 1 mM. These results indicate that phytol has a weak tumor promoter activity compared to TPA and is a non-TPA-type tumor promoter in t his model of mouse skin carcinogenesis.