Production of large amounts of hydrogen peroxide by human tumor cells.
Production of large amounts of hydrogen peroxide by human tumor cells.
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DOI：
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发表时间：
1991-02
期刊：
影响因子：
11.2
通讯作者：
T. Szatrowski;C. Nathan
中科院分区：
文献类型：
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作者：
T. Szatrowski;C. Nathan
已知很少有非吞噬细胞产生活性氧中间体。根据辣根过氧化物酶依赖、过氧化氢酶抑制的荧光东莨菪碱氧化，7个人类肿瘤细胞系以高达0.5 nmol/10(4)个细胞/小时的速率组成H2O2，其累积量在4小时内足以与苯酚酯触发的中性粒细胞产生的H2O2量相当。超氧化物歧化酶抑制铁细胞色素c的还原率要低得多。H2O2的产生被二苯二酮（一种黄蛋白结合剂，浓度产生50%的抑制作用，0.3微米）和二价阳离子螯合剂二乙基二硫代氨基甲酸酯（浓度产生50%的抑制作用，3微米）抑制，但不被氰化物或叠氮化物，电子传递抑制剂，或抑制黄嘌呤氧化酶，多胺氧化酶或细胞色素P450的药物抑制。细胞色素b559存在于人吞噬细胞和淋巴细胞中，用灵敏分光光度法在这些肿瘤细胞中检测不到。转染人酪氨酸酶互补DNA的小鼠成纤维细胞产生黑色素，但不产生H2O2。大量活性氧中间体的组成性生成，如果发生在体内，可能会导致某些肿瘤发生突变，抑制抗蛋白酶，损伤局部组织，从而促进肿瘤的异质性、侵袭和转移。
Few nonphagocytic cells are known to generate reactive oxygen intermediates. Based on horseradish peroxidase-dependent, catalase-inhibitable oxidation of fluorescent scopoletin, seven human tumor cell lines constitutively elaborated H2O2 at rates (up to 0.5 nmol/10(4) cells/h) large enough that cumulative amounts at 4 h were comparable to the amount of H2O2 produced by phorbol ester-triggered neutrophils. Superoxide dismutase-inhibitable ferricytochrome c reduction was detectable at much lower rates. H2O2 production was inhibited by diphenyleneiodonium, a flavoprotein binder (concentration producing 50% inhibition, 0.3 microM), and diethyldithiocarbamate, a divalent cation chelator (concentration producing 50% inhibition, 3 microM), but not by cyanide or azide, inhibitors of electron transport, or by agents that inhibit xanthine oxidase, polyamine oxidase, or cytochrome P450. Cytochrome b559, present in human phagocytes and lymphocytes, was undetectable in these tumor cells by a sensitive spectrophotometric method. Mouse fibroblasts transfected with human tyrosinase complementary DNA made melanin, but not H2O2. Constitutive generation of large amounts of reactive oxygen intermediates, if it occurs in vivo, might contribute to the ability of some tumors to mutate, inhibit antiproteases, injure local tissues, and therefore promote tumor heterogeneity, invasion, and metastasis.