INDUCED MELANIN REDUCES MUTATIONS AND CELL-KILLING IN MOUSE MELANOMA

When melanin absorbs light energy, it can produce potentially damaging active oxygen species, There is little doubt that constitutive pigmen t in dark-skinned individuals is photoprotective against skin cancer, but induced pigment - as in tanning - may not be, The first step in ca ncer induction is mutation in DNA, The most suitable systems for evalu ating the role of melanin are those in which pigment can be varied and mutations can be measured, Several cell lines from Cloudman S91 mouse melanoma can be induced to form large quantities of melanin pigment a fter treatment with a number of different agents enabling comparison o f mutant yields in the same cells differing principally in pigment con centration, In these studies, melanin was induced with synthetic alpha -melanocyte-stimulating hormone and with isobutyl methyl xanthine in t he cell line S91/mel, The former inducer produced about 50% more pigme nt than the latter, Survival and mutation induction at the Na+/K+-ATPa se locus were studied using ethyl methane sulfonate (EMS), a standard mutagen and five UV lamps emitting near monochromatic and polychromati c UV light in the three wavelength ranges of UV. There was greater pro tection against killing and mutation induction in the more heavily pig mented cells after exposure to EMS and after irradiation with monochro matic UVC and UVB, There was significant protection against killing by polychromatic UVB + UVA (FS20), but the small degree of protection ag ainst mutation was not significant, No significant change in killing a nd mutation using the same protocol was seen in S91/amel, a related ce ll line that does not respond to these inducers, No mutants were produ ced by either monochromatic or polychromatic UVA at doses that killed 50% of the cells, Our results show that induced pigment - shown earlie r to be eumelanin (K. A. Cieszka et al., Exp. Dermatol. 4, 192-198, 19 95) - is photo- and chemoprotective, but it is less effective in prote ction against mutagenesis by polychromatic UVB + UVA in a spectrum tha t more nearly approximates the solar spectrum.