Augmentation by L-dopa of growth inhibition and melanin formation of X-irradiated Harding-Passey melanoma cells in culture.
Treatment of exponentially proliferating melanogenic Harding-Passey melanoma cells in monolayer culture (HPM-73 line) with a single dose of X-irradiation (up to 8 Gy) or continuously (for several weeks) with L-3,4-dihydroxyphenylalanine (L-Dopa) up to 5 X 10(-4) M resulted in a dose-dependent inhibition of cell proliferation, but not in death of all cells. Actually, 8 Gy-irradiated or L-Dopa (2 X 10(-4) M)-treated cultures finally reached the cell number and cell density of controls. However, a combination of a single dose of radiation (8 Gy) followed by L-Dopa (2 X 10(-4) M)-treatment resulted in destruction of all cells. Melanin formation was stimulated by L-dopa-treatment or X-irradiation, and was further elevated by the combined application of radiation and L-Dopa-exposure. Whether the effects of exogenously applied L-Dopa, an intermediary metabolite of melanin synthesis, are due to the conversion to growth-inhibitory metabolites (quinones, radicals, etc.) inside or outside the cell, was discussed. The latter might result from release (due to membrane damage or cell disintegration) of tyrosinase or/and melanosomes into the culture medium with the consequence of extracellular synthesis of potentially cytotoxic metabolites from medium substrates. Further, endocytosis of exogenous melanosomes and tyrosinase with potentially harmful effects is feasible. An application of such a combination therapy of melanoma to clinical medicine should be considered.
Schachtschabel
D O
DO
Institut für Physiologische Chemie, Philipps-Universität Marburg.
Pfab
R
R
Paul
N
N
Hess
F
F
D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D066298:In Vitro Techniques; D007980:Levodopa / Q000494:pharmacology*; D008543:Melanins / Q000096:biosynthesis*; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects
D008543:Melanins; D007980:Levodopa