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Metastatic malignant melanoma is considered a chemotherapy-refractory malignancy. A few previous studies have delivered contradictory results regarding the presence and functionality of P-glycoprotein (P-gp), a transmembranous protein associated with the classical multidrug resistance (cMDR), in malignant melanoma. Therefore we have investigated this issue on 33 cell lines established from primary and metastatic lesions of human malignant melanoma, comparing different cMDR detection methods. Immunocytochemically 33% of the cell lines stained positive for P-gp. The data correlated with those of a P-gp-radioimmunometric (antibody-binding) assay. When RT-PCR was used for MDR-1 mRNA determination, 76% of the melanoma cell lines scored positive. Slot-blot analysis was seen to be less sensitive than RT-PCR. Results from the functional P-gp assays, using daunomycin (DM) as MDR-substrate, showed no influence of P-gp expression on drug accumulation and cytotoxicity. However, the cMDR-modifier verapamil (VP) significantly increased both parameters in those melanoma cells with the highest P-gp levels. We conclude that cMDR is apparently not the decisive but probably a complementary protective mechanism against toxic agents in malignant melanoma.

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UVA- and UVB-induced alterations in dermal collagen were investigated in a murine animal model. Groups of hairless mice were exposed to UVA and UVB for 28 weeks at a dose of 60 J/cm2 three times weekly and 0.06 J/cm2 three times weekly, respectively. Untreated animals were used as controls. Every 4 weeks dorsal skin was examined for quantitative and qualitative changes in dermal collagen. Neither UVA nor UVB caused a significant alteration in total skin collagen content. However, after UVA treatment the ability of skin collagen to be digested by pepsin decreased dramatically (up to 65% of skin collagen remained insoluble after 4 months), whereas exposure to UVB had no significant effect. Furthermore a shift in the ratio of alpha 1(I,III) chains to alpha 2(I) chains was detected after UVA exposure. The amount of type V collagen in mouse skin, as determined by a sensitive ELISA method, was markedly decreased after UVA treatment, but not after UVB treatment.