Troll W, Garte S, Frenkel K
Institute of Environmental Medicine, New York University Medical Center, New York 10016.
Basic Life Sci. 1990;52:225-32. doi: 10.1007/978-1-4615-9561-8_19.
Tumor promoters, such as phorbol esters or hormones, cause many biological effects which may contribute to the expression of cancer. The mechanism of cancer expression may have a common theme. One method of learning about this common mechanism is the identification of chemicals that interfere with tumor development. That there is actually a common theme between very different substances, such as inflammatory skin tumor promoters and estradiol causing breast cancer, was shown by the fact that both skin and breast cancers are suppressed by the same agents, e.g., protease inhibitors and retinoids. In addition to skin and breast, protease inhibitors suppress colon, bladder, and liver cancers. The substances that crossed over in suppressing many varieties of cancer were found to inhibit oxygen radical formation by tumor promoter-activated neutrophils and ras oncogene expression in NIH 3T3 cells. Poly(ADP)ribose polymerase (PADPR polymerase) may serve as the connecting link between oxygen radicals that cause its activation and oncogene expression. PADPR polymerase is inhibited by retinoids, antioxidants, and some protease inhibitors. Benzamide, an inhibitor of PADPR polymerase, is also a chymotrypsin inhibitor which suppresses oxygen radical formation by tumor promoter-activated neutrophils. The inhibition of PADPR polymerase causes the expulsion of some oncogenes from NIH 3T3 cells at definite times after oncogene transfection. Further work is required to find what are the contributions of PADPR polymerase to tumor promotion and of its inhibitors to suppression of oncogene expression.
肿瘤促进剂，如佛波酯或激素，会引发许多可能导致癌症发生的生物学效应。癌症发生的机制可能有一个共同的主题。了解这一共同机制的一种方法是识别那些干扰肿瘤发展的化学物质。事实上，非常不同的物质之间存在共同主题，比如炎性皮肤肿瘤促进剂和引发乳腺癌的雌二醇，这一点从皮肤癌和乳腺癌都能被相同的物质（如蛋白酶抑制剂和类视黄醇）抑制得以体现。除了皮肤癌和乳腺癌，蛋白酶抑制剂还能抑制结肠癌、膀胱癌和肝癌。研究发现，能抑制多种癌症的物质可抑制肿瘤促进剂激活的中性粒细胞形成氧自由基以及NIH 3T3细胞中的ras癌基因表达。聚（ADP）核糖聚合酶（PADPR聚合酶）可能是导致其激活的氧自由基与癌基因表达之间的连接环节。PADPR聚合酶受到类视黄醇、抗氧化剂和一些蛋白酶抑制剂的抑制。苯甲酰胺作为PADPR聚合酶的抑制剂，也是一种胰凝乳蛋白酶抑制剂，可抑制肿瘤促进剂激活的中性粒细胞形成氧自由基。抑制PADPR聚合酶会在癌基因转染后的特定时间导致一些癌基因从NIH 3T3细胞中排出。还需要进一步研究以明确PADPR聚合酶对肿瘤促进的作用以及其抑制剂对抑制癌基因表达的作用。
