Modification of dopa toxicity in human tumour cells.
Modification of dopa toxicity in human tumour cells.
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改变多巴对人类肿瘤细胞的毒性。
DOI：
10.1016/0006-2952(85)90652-5
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发表时间：
1985
影响因子：
5.8
通讯作者：
P. Parsons
中科院分区：
文献类型：
--
作者：
P. Parsons
发现多种因素可以改变 1-多巴在 HeLa 细胞 (D3716 μM) 和多巴敏感的非色素人黑色素瘤细胞 (MM96) (D375 μM) 中的毒性，这些细胞具有相似的大小和倍增时间。通过同时使用超氧化物歧化酶、过氧化物酶或过氧化氢酶、通过红细胞或通过缺氧治疗可降低多巴毒性。酶抑制剂l-和d-青霉胺、二乙基二硫代氨基甲酸钠或3-氨基-1,2,4-三唑可增加毒性。两种细胞系的超氧化物歧化酶和过氧化物酶水平相似；在6个人类黑色素瘤细胞系中，多巴杀伤作用与酪氨酸酶活性之间没有相关性，酪氨酸酶活性是通过酪氨酸形成多巴或多巴形成黑色素来确定的。 HeLa 和 MM96 细胞中 1-多巴的摄取相似，并且 2 个细胞系中 1-多巴的毒性与 1-异构体相同。多巴在培养基中 12 小时内分解，速率和产物受添加上述酶和细胞密度的影响。多巴黑色素和含有分解多巴的培养基也对 MM96 细胞具有选择性毒性。以两种不同的方式使用腺病毒 5 来评估 DNA 损伤和多巴抑制 DNA 合成的相对重要性。研究发现，用多巴处理的细胞中病毒复制不受影响，但用 DNA 聚合酶抑制剂阿糖胞苷处理的细胞中病毒复制受到强烈抑制。其次，通过多巴处理 24 小时（D371.3 mM），病毒本身被灭活；在未经处理的 HeLa 或 MM96 细胞中复制经多巴处理的病毒获得了类似的剂量反应曲线。这些结果表明，多巴毒性的初始事件发生在细胞外，并导致形成稳定的有毒产物（可能是黑色素），该产物不会强烈抑制 DNA 聚合酶活性。黑色素瘤过敏并不是由于氧代谢酶、多巴摄取或 DNA 修复的差异造成的。
A variety of factors were found to modify the toxicity ofl-dopa in HeLa cells (D3716 μM) and in dopa-sensitive, nonpigmented human melanoma cells (MM96) (D375 μM) having a similar size and doubling time. Dopa toxicity was decreased by concurrent treatment with superoxide dismutase, peroxidase or catalase, by erythrocytes, or by hypoxia. Toxicity could be increased by the enzyme inhibitorsl- andd-penicillamine, sodium diethyldithiocarbamate or 3-amino-1,2,4-triazole. The two cell lines had similar levels of superoxide dismutase and peroxidase; in 6 human melanoma lines, no correlation was found between dopa killing and tyrosinase activity as determined either by formation of dopa from tyrosine or by formation of melanin from dopa. Uptake ofl-dopa was similar in HeLa and MM96 cells, and the toxicity ofd-dopa was the same in both lines as that of thel-isomer. Dopa decomposed within 12 hr in culture medium, the rate and products being influenced by addition of the above enzymes and by the cell density. Dopa-melanin and medium containing decomposed dopa were also selectively toxic to MM96 cells. Adenovirus 5 was used in two different ways to assess the relative importance of DNA damage and inhibition of DNA synthesis by dopa. Viral replication was found to be unaffected in cells being treated with dopa but was strongly inhibited in cells treated with the DNA polymerase inhibitor cytosine arabinoside. Secondly, the virus was itself inactivated by treatment with dopa for 24 hr (D371.3 mM); similar dose response curves were obtained for replication of dopa-treated virus in untreated HeLa or MM96 cells. These results show that the initial events of dopa toxicity occur outside the cell and lead to the formation of a stable, toxic product (probably melanin) which does not strongly inhibit DNA polymerase activity. Melanoma hypersensitivity was not due to differences in oxygen-metabolizing enzymes, dopa uptake, or DNA repair.
影响因子：
56.9
作者：
KORNER, A;PAWELEK, J
通讯作者：
PAWELEK, J
3,4-二羟基苄胺：一种改进的多巴胺类似物，部分通过抑制 DNA 聚合酶的氧化产物对黑色素瘤细胞具有细胞毒性。
DOI：
10.1111/1523-1747.ep12531751
发表时间：
1983
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
FitzGerald,GB;Wick,MM
通讯作者：
Wick,MM
黄嘌呤氧化酶系统催化的碘化：羟基自由基的作用。
影响因子：
2.9
作者：
Klebanoff,SJ
通讯作者：
Klebanoff,SJ