Parsons P G, Morrison L E
Cancer Res. 1982 Sep;42(9):3783-8.
Six of eight human melanoma lines showed increased sensitivity to killing by dopa and by ascorbate:copper compared with two fibroblast strains and four other human cell lines 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 upon culture conditions, melanoma cells accumulated more [3H]dopa- and [14C]ascorbate-derived isotopic label within the first five min than fibroblasts, but after one hr this difference was less marked. The catalase activity in melanoma cells was not less than that in fibroblasts. Using two independent methods to determine each type of damage, dopa and ascorbate:copper were found to induce DNA breaks in both cell types but not DNA repair synthesis or DNA interstrand cross-links. More DNA breaks were found in melanoma cells (two lines) than in fibroblasts. Semiconservative DNA synthesis was inhibited immediately, recovered within six hr, and in melanoma cells, was again inhibited after 24 hr. RNA synthesis was inhibited less than DNA synthesis. Human cell lines with differential sensitivity to gamma-radiation, ultraviolet light, cross-linking agents, or monofunctional alkylating agents, exhibited normal survival levels when treated with dopa or ascorbate:copper.
与两种成纤维细胞系以及四种其他非黑色素瘤来源的人类细胞系相比，八个人类黑色素瘤细胞系中有六个对多巴以及抗坏血酸盐：铜的杀伤作用表现出更高的敏感性。儿茶酚、肾上腺素和α-甲基多巴（但不包括5,6-二羟基吲哚）表现出类似程度的选择性。当使用短暴露时间或高细胞密度时，毒性会大大降低。根据培养条件，黑色素瘤细胞在前五分钟内积累的[3H]多巴和[14C]抗坏血酸盐衍生的同位素标记比成纤维细胞多，但一小时后这种差异就不那么明显了。黑色素瘤细胞中的过氧化氢酶活性不低于成纤维细胞中的活性。使用两种独立的方法来确定每种类型的损伤，发现多巴和抗坏血酸盐：铜在两种细胞类型中均诱导DNA断裂，但不诱导DNA修复合成或DNA链间交联。在黑色素瘤细胞（两个细胞系）中发现的DNA断裂比成纤维细胞中更多。半保留DNA合成立即受到抑制，在六小时内恢复，并且在黑色素瘤细胞中，24小时后再次受到抑制。RNA合成受到的抑制小于DNA合成。对γ射线、紫外线、交联剂或单功能烷基化剂具有不同敏感性的人类细胞系，在用多巴或抗坏血酸盐：铜处理时表现出正常的存活水平。
