Laboratory probing of oncogenes from human liquid and solid specimens as markers of exposure to toxicants.

Abstract

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.