FUROCOUMARIN-INDUCED EPIDERMAL MELANOGENESIS DOES NOT PROTECT AGAINSTSKIN PHOTOCARCINOGENESIS IN HAIRLESS MICE

Topical 6,4,4'-trimethylangelicin (TMA) plus UVA was used to induce in tense epidermal pigmentation in inbred HRA.HRII-c/+/Skh hairless pigme nted mice over a 13 day period. Subsequent UVB/UVA exposure was used t o assess the photoprotective properties of this tan using skin tumors as an endpoint. Comparisons were always made with sibling albino mice. The TMA/UVA treatment was shown to be not carcinogenic when treated m ice were compared with untreated control mice over 25 weeks. The tan f aded despite daily exposure to UVB/UVA and did not afford any protecti on when TMA/UVA-treated mice with subsequent UVB/UVA were compared wit h pigmented mice treated with UVB/UVA only. In one group, the TMA-indu ced tan was maintained by application of TMA three times a week prior to UVB/UVA for the duration of the experiment. This treatment was asso ciated with a significant increase in tumor risk in both pigmented and albino mice compared to groups treated with UVB/UVA alone, Although p igmented mice had a significant photoprotective advantage, it was show n to be outweighed by the carcinogenic risks of the TMA maintenance tr eatment when they were compared with mice that did not have this treat ment. Nonpretanned pigmented mice developed mild pigmentation during U VB/UVA treatment that was shown to have no protective effect when thos e mice were compared with albinos. We conclude that induced epidermal tanning with or without furocoumarin enhancement is not an effective w ay to prevent skin cancer in the HRA.HRII-c/+/Skh mouse model.