ROLE OF TUMOR SUPPRESSOR GENES AND ONCOGENS IN CHEMICAL CARCINOGENESIS

越来越多的证据表明存在一个肿瘤家族 与不同癌症有关的抑制基因。 使用一种技术 被称为微细胞介导的染色体转移， 分子致癌作用，与Mitsuo Oshimura博士合作 （日本鸟取大学），已经绘制了参与肿瘤抑制基因的图谱， 人类和啮齿动物1号染色体的癌症（子宫内膜癌， 纤维肉瘤），3号染色体（肾癌，肺癌），6号染色体 （子宫内膜癌），染色体7（绒毛膜癌），染色体9 （子宫内膜癌）和11号染色体（宫颈癌，Wilms肿瘤， 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 映射到不同的染色体上; 2）一个以上的正常染色体 可以抑制给定肿瘤系的致瘤性，这表明， 多种肿瘤抑制基因参与某些肿瘤（例如， 子宫内膜癌的1、6和9号染色体和子宫内膜癌的3和11号染色体。 肺腺癌）; 3）可以观察到性别剂量效应（即，一 一个抑制染色体的拷贝可以抑制某些肿瘤;其他肿瘤 需要两个拷贝）;和4）功能上不同肿瘤抑制因子 可以鉴定基因（致瘤性的抑制可以发生在 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).