MOLECULAR BASIS FOR CELLULAR CHANGES IN CHEMICAL CARCINOGENESIS

叙利亚仓鼠胚胎(SHE)细胞的肿瘤发育是一个多步骤的过程 进程。然而，步骤的数量和所涉及的基因或变化 都是未知的。我们比较了正常和正常的易感性 致癌物诱导癌前SHE细胞转化 用致癌病毒基因组克隆的质粒组：多发性瘤 病毒、哈维小鼠肉瘤病毒(v-Ha-ras)和MC29病毒(pSVv-myc)。 转染多瘤病毒DNA的正常SHE细胞在体内形成肿瘤 裸鼠皮下注射3-4周。相比之下，SHE细胞 对于v-Ha-ras，DNA保持非致瘤性。转染SHE细胞的研究进展 V-Ha-ras DNA+v-myc DNA形成潜伏期短的肿瘤。 这些结果表明，多种改变或激活的癌基因是 是肿瘤转化所必需的。以确定是否 Ras和myc的激活足以促进肿瘤的发生，我们进行了 转叙利亚人成瘤细胞的细胞遗传学分析 含有v-Ha-ras和v-myc DNA的仓鼠胚胎细胞或仅有多瘤DNA的仓鼠胚胎细胞。 而多瘤诱导的肿瘤来源的细胞是二倍体的，诱导的是肿瘤 V-Ha-ras加v-myc的癌基因是单克隆性的，具有非随机的 染色体改变，15号染色体的单体。因此，额外的改变， 15号染色体的丢失是肿瘤发生所必需的或有利的 由v-Ha-ras加v-myc癌基因诱导。这些结果表明， 正常的二倍体细胞的肿瘤进展需要两个以上的 在特定条件下的步数。以确定正常的细胞因子或 基因可以调节致瘤性和/或表型的表达 癌基因，化学转化的SHE细胞和SHE细胞之间的细胞-细胞杂交 制备正常或癌前病变的SHE细胞。锚地 自主性和致瘤性在杂交种中被抑制 致瘤细胞和正常细胞以及致瘤细胞和MOST的杂交 但并不是所有的癌前细胞。这表明这种压抑 在肿瘤进展过程中可能会丧失能力，这代表着一步 在这个过程中。

Neoplastic development of Syrian hamster embryo (SHE) cells is a multistep process. However, the number of steps and the genes or changes involved are unknown. We have compared the susceptibilities of normal and carcinogen-induced preneoplastic SHE cells to transformation following transfection with plasmids of genomic clones of oncogenic viruses: polyoma virus, Harvey murine sarcoma virus (v-Ha-ras), and MC29 virus (pSVv-myc). Normal SHE cells transfected with polyoma virus DNA formed tumors within 3-4 weeks when injected into nude mice. In contrast, SHE cells treated with v-Ha-ras DNA remained nontumorigenic. SHE cells transfected with v-Ha-ras DNA plus v-myc DNA formed tumors with short latency periods. These results suggest that multiple changes or activated oncogenes are required for the neoplastic transformation. To determine whether activation of ras plus myc was sufficient for tumorigenicity, we performed cytogenetic analyses of tumors formed following transfection of Syrian hamster embryo cells with v-Ha-ras plus v-myc DNAs or polyoma DNA alone. Whereas polyoma-induced, tumor-derived cells were diploid, tumors induced by v-Ha-ras plus v-myc oncogenes were monoclonal and had a nonrandom chromosome change, monosomy of chromosome 15. Thus, an additional change, loss of chromosome 15, is required or advantageous for tumorigenicity induced by v-Ha-ras plus v-myc oncogenes. These results suggest that neoplastic progression of normal, diploid cells requires more than two steps under certain conditions. To determine if normal cellular factors or genes can regulate the phenotypic expression of tumorigenicity and/or oncogenes, cell-cell hybrids between chemically transformed SHE cells and either normal or preneoplastic SHE cells were prepared. Anchorage independence and tumorigenicity were suppressed in hybrids between tumorigenic and normal cells and in hybrids between tumorigenic and most but not all preneoplastic cells. This suggests that this suppressive ability may be lost during neoplastic progression and represents one step in this process.