ROLE OF MUTAGENESIS IN CARCINOGENESIS

大多数化学致癌物会导致DNA损伤，并在特定情况下具有致突变性 遗传基因；然而，某些致癌物质(包括人类致癌物质 己烯雌酚(DES)、石棉、砷化合物和苯)通常不会 诱发基因突变。我们已经检查了这些化学物质的能力 诱发形态转化、基因突变和染色体 叙利亚仓鼠胚胎(SHE)细胞培养中的突变。我们有 以前提出的DES的作用机制与其 诱发染色体数目变化的能力，即非整倍体。 目前，DES诱导的非整倍体正在新生小鼠中进行检测。 以测试这些变化是否发生在体内的目标生殖道 组织。另一种重要的人类致癌物质石棉的作用机理是 也进行了检查。我们已经提出石棉可以诱导细胞转化。 因为它有能力引起染色体的变化。我们已经确定了一个 人间皮瘤中可能存在新的转化癌基因，目前 我们正在克隆这个基因。亚砷酸钠和亚砷酸钠不起作用。 作为基因诱变剂，但是细胞转化的有效诱导剂，但 弱基因诱变剂。这种化学物质是非常有效的非整倍体诱导剂。 在这个系统中。这些结果进一步支持了我们的假设 转化涉及一种染色体突变，并暗示了一种重要的 致癌物诱导的非整倍体在癌变中的作用。DI(2- 邻苯二甲酸乙基己酯(DEHP)，一种常用的塑化剂，导致 肝细胞和肝细胞癌中过氧化物酶体增殖的研究 啮齿动物。我们已经证明了DEHP可以诱导形态转化， 培养的叙利亚人的染色体异常和过氧化物酶增殖体 仓鼠胚胎(SHE)细胞。转化频率和染色体 在大鼠活体后，DEHP的像差增强。 线粒体上清液。结果表明，可能出现了 DEHP代谢物诱导转化过程中的遗传损伤 她的细胞。过氧酶体的诱导没有明确的关系 观察细胞增殖和细胞转化情况。

Most chemical carcinogens induce DNA damage and are mutagenic at specific genetic loci; however, certain carcinogens (including the human carcinogens diethylstilbestrol (DES), asbestos, arsenicals and benzene) usually do not induce gene mutations. We have examined the ability of these chemicals to induce morphological transformation, gene mutations and chromosome mutations in Syrian hamster embryo (SHE) cells in culture. We have previously proposed that the mechanism of action of DES is related to its ability to induce numerical chromosome changes, i.e., aneuploidy. Currently, DES-induced aneuploidy is being examined in the newborn mouse genital tract to test whether these changes occur in vivo in the target tissue. The mechanism of another important human carcinogen, asbestos, was also examined. We have proposed that asbestos induces cell transformation due to its ability to induce chromosomal changes. We have identified a possibly novel transforming oncogene in human mesotheliomas, and currently we are cloning this gene. Sodium arsenite and sodium arsenate are inactive as gene mutagens but are potent inducers of cell transformation but is a weak gene mutagen. This chemical is a very effective inducer of aneuploidy in this system. These results further support our hypothesis that cell transformation involves a chromosomal mutation and suggest an important role for carcinogen-induced aneuploidy in carcinogenesis. Di(2- ethylhexyl)phthalate (DEHP), a commonly used plasticizer, induces peroxisome proliferation n liver cells and hepatocellular carcinomas in rodents. We have shown that DEHP induces morphological transformation, chromosome aberrations, and peroxisome proliferations of cultured Syrian hamster embryo (SHE) cells. The transformation frequency and chromosomal aberrations of DEHP was enhanced in the presence of rat live post- mitochondrial supernatant. The results suggest a possible invovement of genetic damage by DEHP metabolites in the induction of transformation of SHE cells. No clear relationship between induction of peroxisome proliferation and cell transformation was observed.