A Multitherapy Resistance Factor From Melanoma Reveals That Killing by Near Uv Is Different From Genotoxic Agents

A diffusible multitherapy resistance factor (MTRF) is produced by Cloudman S91 melanoma cells in vitro. The MTRF decreases sensitivity of the target cell line, S91/amel, to gamma-irradiation, UVC (200-280 nm) and mitomycin C (MMC). In the present study, we demonstrate that MTRF also increases the survival of S91/amel after exposure to actinomycin D (AMD) and vinblastine (VBL). The MTRF is thus effective when target cells have been exposed to five genotoxic agents that act by different mechanisms. It does not alter the response to the same five agents of the S91/I3 producer cells, which are presumably saturated with the factor. The factor has no effect on the survival of S91/amel cells that have been exposed to lethal doses of near monochromatic UVB (280-320 nm) or UVA (320-400 nm) or to polychromatic FS20 lamps. The lack of effectiveness of MTRF after cells have been exposed to near (300-400 nm) UV radiation indicates that in this wavelength range, S91 melanoma cells are killed by mechanisms that are different from the lethal effects of the five genotoxic agents (gamma-irradiation, UVC, MMC, AMD and VBL) to which the target cells demonstrate a response.