MALIGNANT CONVERSION OF MOUSE SKIN TUMORS IS INCREASED BY TUMOR INITIATORS AND UNAFFECTED BY TUMOR PROMOTERS
MALIGNANT CONVERSION OF MOUSE SKIN TUMORS IS INCREASED BY TUMOR INITIATORS AND UNAFFECTED BY TUMOR PROMOTERS
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DOI：
10.1038/304067a0
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发表时间：
1983-01-01
期刊：
影响因子：
64.8
通讯作者：
YUSPA, SH
中科院分区：
文献类型：
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作者：
HENNINGS, H;SHORES, R;YUSPA, SH
多阶段癌变（起始-促进）首先在小鼠皮肤中被证实1,2。第一阶段，启动，是通过低剂量的致癌物来完成的，不会引起肿瘤。用某些非致癌性增生性药物反复治疗启动小鼠，导致大量良性乳头状瘤的快速产生，其中少数发展为鳞状细胞癌。虽然这个模型系统产生的大多是良性肿瘤，但许多关于上皮组织癌变的概念来源于小鼠皮肤研究。肿瘤启动物对生长潜力的永久性改变通常被认为是一个致突变事件3；启动细胞的细胞选择和克隆扩增可能参与了促进作用4。在起始-促进实验中，90%以上的鳞状细胞癌由乳头状瘤发展而来5,6，但转换率很低。良性肿瘤向恶性肿瘤转化的必要因素尚未确定，但假定肿瘤启动子参与其中。然而，我们在这里报告了肿瘤启动子12- o-十四烷醇-磷酸-13-乙酸酯（TPA）在乳头状瘤向癌的转化中无效，而三种引发剂，聚氨酯，n -甲基-n ' -硝基-n -亚硝基胍（MNNG）和4-硝基喹啉-n -氧化物（4-NQO）是有效的。这表明，恶性转化可能是由乳头状瘤细胞进一步的遗传变化引起的，TPA的无效可能是由于其作为诱变剂的不活性。
Multi-stage carcinogenesis (initiation–promotion) was first demonstrated in mouse skin1,2. The first stage, initiation, is accomplished by a low dose of carcinogen that causes no tumours. Promotion by repeated treatment of initiated mice with certain non-carcinogenic hyperplastic agents results in the rapid production of numerous benign papillomas, a few of which progress to squamous cell carcinomas. Although this model system produces mostly benign tumours, many of the concepts concerning carcinogenesis in epithelial tissues have been derived from mouse skin studies. The permanent change in growth potential accomplished by tumour initiators is generally considered to be a mutagenic event3; cell selection and clonal expansion of initiated cells may be involved in promotion4. In initiation–promotion experiments, more than 90% of the squamous cell carcinomas develop from papillomas5,6, but the conversion rate is low. The factors necessary for this conversion of benign to malignant tumours have not been defined but tumour promoters have been assumed to be involved. However, we report here that the tumour promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) is ineffective in the conversion of papillomas to carcinomas whereas three initiators, urethane, N-methyl-N′-nitro-N-nitrosoguanidine ((MNNG) and 4-nitroquinoline-N-oxide (4-NQO) are effective. This suggests that malignant conversion may result from a further genetic change in papilloma cells and that the ineffectiveness of TPA may be due to its inactivity as a mutagen.