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Sensitivity of Human Melanoma Cells to L-Dopa and DL-Buthionine (S,R)-sulfoximine¹

Queensland Institute of Medical Research, Herston, Queensland, Australia 4006

Four of seven human melanoma cell lines were sensitive to killing by L-dopa (D₃₇ 1.0–4.7 µM) compared with fibroblasts, Hela, and three ovarian tumor cell lines (D₃₇ 12–59 µM). All seven melanoma lines, however, were sensitive to DL-buthionine(S,R)sulfoximine (BSO) (D₃₇ 0.73–8.5 µM) compared with the nonmelanoma cells (D₃₇ 25–68 µM). The melanoma line most sensitive to BSO (MM418) was highly melanized, proliferated slowly and was resistant to other agents [dopa, 5-(3-methyl-1-triazeno)5-imidazole-4-carboxamide, melphalan, methotrexate, hydroxyurea, etoposide, Adriamycin]. In most cell lines, L-dopa and BSO blocked cell proliferation in all phases of the cell cycle. Cellular sensitivity to dopa or BSO did not correlate with levels of total soluble SH, glutathione (GSH), GSH reductase, GSH peroxidase or GSH transferase, or with the extent of GSH depletion induced by the drug. No GSH transferase activity could be detected in the dopa-resistant HeLa line, indicating that detoxification of quinones is not an important mechanism of resistance. Within the group of melanoma cell lines, sensitivity to dopa correlated with decreased level of -glutamyl transpeptidase (r = 0.81). However, the -glutamyl transpeptidase inhibitor azaserine was less effective than BSO in enhancing the toxicity of dopa. It can be inferred that (a) there is no simple relationship between GSH metabolism and sensitivity to dopa or BSO in human melanoma cells, and (b) BSO may be an effective agent for melanoma.

¹ This work was supported by a grant from the National Health and Medical Research Council, Canberra, Australia.

² Present address: Department of Applied and Engineering Physics, Cornell University, Ithaca, NY 14853.

³ To whom requests for reprints should be addressed, at Queensland Institute of Medical Research, Bramston Terrace, Herston, Brisbane, Queensland, Australia 4006.

Received 11/12/87. Revised 11/ 8/88. Accepted 2/ 1/89.