The system of DNA-mediated genetic transformation that is now functional in this laboratory involves the transfer of human genes of APRT and HPRT into enzyme-deficient mouse cells. The system will be elaborated with regard to the usable types of DNA donor and recipient cells, with regard to the loci that can be transferred and with regard to improving the efficiency from 10 to the minus 7th power to 10 to the minus 6th power per recipient cell to at least 10 to the minus 5th power per recipient cell. If the donated piece of DNA replicates but is not integrated into the recipient cell genome we will attempt to clone the human APRT and HPRT genes using Charon phage or PBR-322 plasmid vectors. Cell hybridization procedures will be used to determine if permanent line character, malignancy-related morphological transformation, anchorage-independent growth and tumorigenicity are dominantly expressed in combinations of human cells, combination of mouse cells and mouse-human combinations. We will attempt to isolate possible chromosomes and genes that are responsible for dominantly expressed malignancy traits by transfer of microcells, metaphase chromosomes, interphase chromatin and DNA. If transfer of small pieces of genetic material are successful we will attempt to clone the responsible genes.