Review: gene amplification--a cellular response to genotoxic stress.

Molecular toxicology Pub Date : 1989-10-01
C Lüke-Huhle
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Abstract

Recent years of cancer research have defined the role of key regulatory genes in oncogenesis. Oncogenes and suppressor genes are affected in the process of carcinogenesis either by mutations within the coding region, promoter mutations, or gene amplification. This review describes our studies on gene amplification in mammalian cells, with emphasis on the initiating events induced by carcinogenic chemicals and various types of radiation. The influence of genomic instability, cell dedifferentiation, and the malignant potential of a cell on their capacity to amplify genes is demonstrated by molecular biologic and cytogenetic studies on human and rodent cells. Cells that contain amplified DNA are at risk for chromosomal aberrations, sister chromatid exchanges, and rearrangements. Surviving cells show such cancer-prone genetic consequences.

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综述:基因扩增——对基因毒性应激的细胞反应。
近年来的癌症研究明确了关键调控基因在肿瘤发生中的作用。致癌基因和抑制基因在癌变过程中受到编码区突变、启动子突变或基因扩增的影响。本文综述了我们在哺乳动物细胞中基因扩增的研究,重点介绍了致癌化学物质和各种类型辐射诱导的启动事件。对人类和啮齿动物细胞进行的分子生物学和细胞遗传学研究证明了基因组不稳定性、细胞去分化和细胞的恶性潜能对其基因扩增能力的影响。含有扩增DNA的细胞存在染色体畸变、姐妹染色单体交换和重排的风险。存活的细胞显示出这种易患癌症的遗传后果。
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Xenobiotic regulation of glutathione S-transferase Ya gene expression. Review: gene amplification--a cellular response to genotoxic stress. Limitations of the fluorescent probe viability assay. Induction of a novel damage-specific DNA binding protein correlates with enhanced DNA repair in primate cells. Induction of a novel damage-specific DNA binding protein correlates with enhanced DNA repair in primate cells.
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