DNA DAMAGE AND SELECTIVE TOXICITY OF DOPA AND ASCORBATE - COPPER IN HUMAN-MELANOMA CELLS

  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (9) , 3783-3788
Abstract
Of 8 human melanoma lines [MM96, MM127, MM138, MM170, MM200, MM214, MM229, MM253c], 6 showed increased sensitivity to killing by dopa and by ascorbate:copper compared with 2 fibroblast strains [MBP, PGP] and 4 other human cell lines [cervical carcinoma HeLa S3, lymphoblastoid DJM, ataxia telangiectasia ST and xeroderma pigmentosum GM 2250] of nonmelanoma origin. Catechol, epinephrine and .alpha.-methyldopa, but not 5,6-dihydroxyindole, exhibited a similar degree of selectivity. Toxicity was greatly reduced when brief exposure times or high cell densities were used. Depending on culture conditions, melanoma cells accumulated more [3H]dopa- and [14C]ascorbate-derived isotopic label within the first 5 min than fibroblasts, but after 1 h this difference was less marked. The catalase activity in melanoma cells was not less than that in fibroblasts. Using 2 independent methods to determine each type of damage, dopa and ascorbate:copper induced DNA breaks in both cell types but not DNA repair synthesis or DNA interstrand cross-links. More DNA breaks were found in melanoma cells (2 lines) than in fibroblasts. Semiconservative DNA synthesis was inhibited immediately, recovered within 6 h, and in melanoma cells was again inhibited after 24 h. RNA synthesis was inhibited less than DNA synthesis. Human cell lines with differential sensitivity to .gamma.-radiation, UV light, cross-linking agents, or monofunctional alkylating agents exhibited normal survival levels when treated with dopa or ascorbate:copper.