Differential sensitivity of human normal and malignant cells to 8-azahypoxanthine in vitro

Abstract

Human fibroblast strains in vitro are markedly resistant to medium containing levels of 8-azahypoxanthine (AH) which are lethal to malignant cells. This difference depends on the presence of hypoxanthine in the fetal calf serum used to make standard tissue culture medium. Although malignant cells in culture possess approximately three times more effective hypoxanthine-guanine phosphoribosyl transferase (HGPRT) activity than normal cells, this does not account for the protective action of hypoxanthine in the latter. Rather, our data, together with that of others, suggest that hypoxanthine protects normal cells from AH by preventing its reaction with phosphoribosyl pyrophosphate via HGPRT. Whether this is the consequence of a qualitative difference between the HGPRT's of malignant and normal cells or a reflection of differential permeability to hypoxanthine requires further experimentation.