The roles of morphogenetic differentiation in controlling the phenotypic expression of neoplastic transformation, the degree of malignancy of tumors, and the susceptibility of developing organs to carcinogenesis are studied using organ culture and tissue transplantation techniques, with current emphasis on the kidney. A defined medium for growth of rat and mouse ureteric bud epithelium in monolayer culture has been developed in which epidermal growth factor and selenium have proved essential and insulin, hydrocortisone, and transferrin have proved highly beneficial. The ability of transplacentally administered carcinogens to induce genotoxic damage in cells of embryos or fetuses exposed at different stages of gestation was determined for rat, mouse, and Syrian hamster. Cells were isolated from exposed embryos and gene mutations at two to three loci (resistance to ouabain and 6-thioguanine, and to diphtheria toxin in the hamster) were assayed in vitro with simultaneous determination of survival ability. Organ specificity of induced gene mutation is being determined in embryonal cells isolated from organs of various species exposed in utero at comparable stages of gestation. A maximum level of mutation induction was found to be inducible by N-nitrosoethylurea at day 9 of gestation for mesenchymal cells of the Syrian hamster and at day 9-10 for the F344 rat.
