Zimmerman R, Cerutti P
Proc Natl Acad Sci U S A. 1984 Apr;81(7):2085-7. doi: 10.1073/pnas.81.7.2085.
There is much evidence from in vivo and in vitro carcinogenesis studies that active oxygen species play a role in tumor promotion. We tested directly whether superoxide produced extracellularly by xanthine-xanthine oxidase (X-XO) has the capacity to promote initiated mouse embryo C3H/10T1/2 fibroblasts. Cell cultures initiated with either 137Cs gamma-rays or benzo[a]pyrene diol epoxide I were found to transform 3-30 times more effectively when subsequently treated daily for 3 weeks with nontoxic doses of X-XO. Scavengers of active oxygen radicals such as superoxide dismutase or superoxide dismutase in combination with catalase reduced the frequency of appearance of transformed foci by 3-25 times when compared to cultures receiving X-XO alone. These results show that active oxygen species such as superoxide and H2O2 can act in a promotional manner that mimics the effects of the mouse skin promoter phorbol 12-myristate 13-acetate in this system. X-XO also acted as a weak complete carcinogen.
体内和体外致癌研究有大量证据表明活性氧在肿瘤促进过程中发挥作用。我们直接测试了黄嘌呤 - 黄嘌呤氧化酶（X - XO）在细胞外产生的超氧化物是否有能力促进已启动的小鼠胚胎C3H/10T1/2成纤维细胞的转化。在用137Csγ射线或苯并[a]芘二醇环氧化物I启动细胞培养后，发现随后用无毒剂量的X - XO每日处理3周时，细胞转化效率提高了3至30倍。与单独接受X - XO处理的培养物相比，超氧化物歧化酶或超氧化物歧化酶与过氧化氢酶组合等活性氧自由基清除剂使转化灶出现频率降低了3至25倍。这些结果表明，超氧化物和过氧化氢等活性氧可以以一种促进方式起作用，在此系统中模拟小鼠皮肤促进剂佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯的作用。X - XO还可作为一种弱的完全致癌物。
