Genetic markers in mouse teratocarcinoma cells. Selection and partial characterization of mutants resistant to toyocamycin, DRB and podophyllotoxin

Stable mutants resistant to a number of cytotoxic drugs, (i) adenosine analog toyocamycin (Toyr); (ii) microtubule inhibitor podophyllotoxin (PodR); and (iii) nucleoside analog 5,6-dichloro-1-β-d-ribofuranosyl benzimidazole (DrbR), have been isolated in the mouse teratocarcinoma cell line OC15S1. Biochemical studies reveal that the genetic lesion in Toyr mutants causes a nearly total deficiency of the enzyme adenosine kinase, which phosphorylate adenosine and its analogs and plays an important role in purine nucleotides metabolism. The lesions in PodR and DrbR classes of mutants have not yet been fully characterized. The availability of these new genetic markers in mouse teratocarcinoma cells should make it possible to examine the role of the affected functions in vivo in an intact organism.