Action of 2-beta-d-Ribofuranosylthiazole-4-carboxamide (tiazofurin) in Chinese hamster ovary and variant cell lines.

The metabolism and inhibitory activity of 2-beta-D-ribofuranosylthiazole-4-carboxamide (tiazofurin, RTC, NSC 286193) was studied in Chinese hamster ovary (CHO) cells and a series of mutants derived from them. Isotope incorporation experiments indicate dramatic inhibition of DNA and RNA synthesis by tiazofurin but little or no effect on protein synthesis. In CHO cells, tiazofurin is more toxic than ribavirin and also demonstrates a stronger inhibition of guanine nucleotide synthesis. Tiazofurin is phosphorylated by crude extracts of CHO cells. Variant cell lines lacking adenosine kinase (EC 2.7.1.20) or deoxycytidine kinase (EC 2.7.1.74) show no resistance to tiazofurin, suggesting that these enzymes are not responsible for the phosphorylation of tiazofurin. The inhibitory activity of this agent can be reversed by exogenously supplied guanine, suggesting that the inhibition is due, at least in part, to guanylate deficiency.