UVA, pheomelanin and the carcinogenesis of melanoma

Cloudman S91 mouse melanoma cells var!, in constitutive and inducible melan in levels. Survival, mutation induction and DNA damage a ere quantitated af ter exposure to UVB, UVA and FS20 lamps. Assuming that the observed differe nces are related to melanin, induced pigment is photo-protective for surviv al and mutation after UVB and FS20 exposure, and is photosensitizing for su rvival after UVA exposure, No changes in pyrimidine dimers could be measure d. DNA damage in pigmented mouse melanocytes (melan-a and melan-b) was grea ter than that in albino melanocytes (melan-c) after UVB and FS20, and the p igmented cells were moro sensitive to killing. Pigment appears to be protec tive for killing by UVA in these melanocytes. Human melanocytes from differ ent skin h-pes vary in both melanin amount and composition (eu- and pheomel anin). Effects of pigmentation on UVB responses are unclear. In UVA, heavil y pigmented cells have more DNA damage than lightly pigmented cells, but ar e resistant to killing. Increased pheomelanin photosensitizes DNA damage in lightly pigmented cells, Since eumelanin predominates in the mouse melanom a cells and melanocytes, they are less likely than human cells to provide a satisfactory model for human solar melanomagenesis, In order to understand the mechanism of photocarcinogenesis of melanoma, melanins in human melano cytes from different pigment types should be carefully quantitated and char acterized. Mutations induced in them by solar wavelength-emitting lamps wit h cell-characterized spectra should be measured, and mutant DNA should be s equenced to determine the nature of the solar-induced lesions. Research sho uld focus on UVA and pheomelanin.