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。 过程 然而，步骤的数量和涉及的基因或变化 是未知的。 我们比较了正常和 致癌物诱导的癌前SHE细胞转化， 用致癌病毒基因组克隆质粒转染：多瘤病毒 病毒、哈维鼠肉瘤病毒（v-Ha-ras）和MC 29病毒（pSVv-myc）。 用多瘤病毒DNA转染的正常SHE细胞在 3-4当注射到裸鼠体内时， 相反，SHE细胞处理 而v-Ha-ras DNA则无致瘤性。 转染SHE细胞， v-Ha-ras DNA加v-myc DNA形成的肿瘤潜伏期短。 这些结果表明，多种变化或激活的癌基因是 肿瘤转化所需的。 以确定是否 ras + myc的激活足以致瘤，我们进行了 转染Syrian后形成的肿瘤的细胞遗传学分析 仓鼠胚胎细胞与v-Ha-ras加v-myc DNA或单独的多瘤DNA。 然而，多瘤诱导的肿瘤衍生细胞是二倍体，肿瘤诱导的细胞是二倍体。 v-Ha-ras和v-myc癌基因是单克隆的，具有非随机性， 染色体改变，15号染色体单体。 因此，另一个变化是， 15号染色体的缺失是致瘤性所必需的或有利的 由v-Ha-ras和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 在一定条件下的步骤。 以确定是否正常的细胞因子或 基因可以调节致瘤性的表型表达和/或 癌基因，化学转化的SHE细胞之间的细胞-细胞杂交， 制备正常或肿瘤前SHE细胞。 锚固 独立性和致瘤性在杂交种中受到抑制， 在致瘤细胞和正常细胞之间以及在致瘤细胞和大多数细胞之间的杂交中， 但不是所有的癌前细胞。 这表明这种抑制性的 在肿瘤进展过程中可能丧失这种能力， 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.