ROLE OF TUMOR SUPPRESSOR GENES AND ONCOGENS IN CHEMICAL CARCINOGENESIS

越来越多的证据表明存在一种肿瘤家族 参与不同癌症的抑制基因。使用一种技术 被称为微细胞介导的染色体转移，该实验室 分子癌变，与大村三夫博士合作 (日本鸟取大学)，已经绘制了涉及 人类和啮齿动物癌症到1号染色体(子宫内膜癌， 纤维肉瘤)，染色体3(肾癌、肺癌)，6号染色体 (子宫内膜癌)，7号染色体(绒毛膜癌)，9号染色体 (子宫内膜癌)和11号染色体(宫颈癌、肾母细胞瘤、 横纹肌肉瘤、肺癌、纤维肉瘤)。这些研究表明1) 肿瘤抑制基因家族的不同成员可以是 被定位到不同的染色体上；2)不止一个正常染色体 可以抑制特定肿瘤株的致瘤性，这表明 某些肿瘤涉及多个肿瘤抑制基因(例如， 第1、6和9号染色体为子宫内膜癌，第3和11号染色体为 肺腺癌)；3)可以观察到遗传剂量效应(即 抑制染色体的复制可以抑制某些肿瘤；其他肿瘤 需要两个拷贝)；以及4)功能不同的肿瘤抑制因子 可以识别基因(或可发生致瘤性抑制 没有细胞衰老或生长抑制)。

There is increasing evidence for the existence of a family of tumor suppressor genes that are involved in different cancers. Using a technique known as microcell-mediated chromosome transfer, the Laboratory of Molecular Carcinogenesis, in collaboration with Dr. Mitsuo Oshimura (Tottori University, Japan), has mapped tumor suppressor genes involved in human and rodent cancers to chromosome 1 (endometrial cancer, fibrosarcomas), chromosome 3 (renal cancer, lung cancer), chromosome 6 (endometrial cancer), chromosome 7 (choriocarcinoma), chromosome 9 (endometrial cancer), and chromosome 11 (cervical cancer, Wilms' tumor, rhabdomyosarcoma, lung cancer, fibrosarcoma). These studies have shown 1) that different members of the family of tumor suppressor genes can be mapped to different chromosomes; 2) that more than one normal chromosome can suppress the tumorigenicity of a given tumor line, which indicates that multiple tumor suppressor genes are Involved in certain tumors (e.g., chromosomes 1, 6, and 9 i endometrial cancer and chromosomes 3 and 11 in lung adenocarcinoma); 3) that gen dosage effects can be observed (i.e., one copy of a suppressing chromosome can suppress certain tumors; other tumors require two copies); and 4) that functionally distinct tumor suppressor genes can be identified (suppression of tumorigenicity can occur with or without cellular senescence or growth suppression).