Nelson E
Toxicology Laboratory, University Medical Center, Essen, Germany.
Crit Rev Toxicol. 1996 Sep;26(5):483-549. doi: 10.3109/10408449609037476.
Recent discoveries regarding the mechanistic role of oncogenes and tumor suppressor genes in cancer development have opened a new era of molecular diagnosis. It has been observed repeatedly that genetic lesions serve as tumor markers in a broad variety of human cancers. The ras gene family, consisting of three related genes, H-ras, K-ras, and N-ras, acquires transforming activity through amplification or mutation in many tissues. If not all, then most types of human malignancies have been found to contain an altered ras gene. Because the ras oncogenes actively participate in both early and intermediate stages of cancer, several highly specific and sensitive approaches have been introduced to detect these genetic alterations as biomarkers of exposure to carcinogens. There is also mounting evidence that implicate chemical-specific alterations of the p53 tumor suppressor gene detected in most human tumors. Therefore, it seems a reliable laboratory approach to identify both altered p53 and ras genes as biomarkers of human chronic or intermittent exposure to toxicants in a variety of occupational settings.
近期关于癌基因和肿瘤抑制基因在癌症发展中的机制作用的发现开启了分子诊断的新时代。人们反复观察到，基因损伤在多种人类癌症中作为肿瘤标志物。由三个相关基因H-ras、K-ras和N-ras组成的ras基因家族，通过在许多组织中的扩增或突变获得转化活性。已发现如果不是所有类型，那么大多数人类恶性肿瘤都含有改变的ras基因。由于ras癌基因积极参与癌症的早期和中期阶段，已引入了几种高度特异性和敏感性的方法来检测这些基因改变，作为接触致癌物的生物标志物。也有越来越多的证据表明，在大多数人类肿瘤中检测到的p53肿瘤抑制基因的化学特异性改变。因此，将改变的p53和ras基因都鉴定为人类在各种职业环境中慢性或间歇性接触毒物的生物标志物，似乎是一种可靠的实验室方法。
