DEVELOPMENT AND UTILIZATION OF THE RAT LYMPHOCYTE HPRT MUTATION ASSAY

Much of the recent progress in the field of genetic toxicology has com e from an increased understanding of the molecular and cellular biolog y of the mammalian organism. Most prominent has been the ability to de tect and quantify somatic mutation and relate the nature of the mutati on to the specific type of chemical damage. Building upon the foundati on of the human lymphocyte hypoxanthine guanine phosphoribosyl transfe rase (hprt) system, and later, the mouse hprt system, methods for the detection and quantification of hprt mutations in rat lymphocytes were developed. These methods are described in this report as is the ongoi ng validation of the assay. Additionally, the characterization of the recovered mutants and a comparison of the mutation spectrum in the rat lymphocyte system to the spectrum in cancer genes, such as H-ras and p53, and the spectrum in transgenic systems, such as IacI, are include d. The development of the rat lymphocyte hprt system and validation of the assay at the molecular level, provide an effective and reliable m easure of genetic damage in an in vivo system which is readily compara ble to measurement of genetic damage in the human. (C) 1997 Elsevier S cience B.V.