Altered Enzymes in Drug-Resistant Variants of Mammalian Tissue Culture Cells

Two selective procedures are compared in an effort to isolate variants of mouse L cells containing structural gene mutations. Among the resulting variant cloned cell lines are found two types of alterations in the enzyme hypoxanthine phosphoribosyl transferase (EC 2.4.2.8) (1): enzyme with altered kinetic constants causing in vivo and in vitro resistance to 8-azaguanine; and (2) enzyme with altered heat sensitivity in vitro. These results support the view that tissue culture cell variants can arise from structural gene mutations.