A cytotoxic effect associated with 9-(1,3-dihydroxy-2-propoxymethyl)-guanine is observed during the selection for drug resistant human cells containing a single herpesvirus thymidine kinase gene.
A cytotoxic effect associated with 9-(1,3-dihydroxy-2-propoxymethyl)-guanine (DHPG) was discovered while searching for spontaneous mutations in a single copy, integrated HSV-1 thymidine kinase (TK) gene in the human 143 TK- cell line. It was found that spontaneous DHPGR mutations could not be selected while other anti-TK drugs resulted in selectable mutation frequencies of 10(-4) to 10(-3). When 143 TK- cells were mixed with these HSV-1 TK+ cells and subjected to DHPG, a 90% to 100% decrease in recoverable TK- colonies was observed. In addition, the media from the HSV-1 TK+ cells metabolizing DHPG was shown to inhibit the growth of the TK- cells.
D000212:Acyclovir / Q000031:analogs & derivatives* / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004351:Drug Resistance; D015774:Ganciclovir; D006564:Herpesviridae / Q000201:enzymology*; D006801:Humans; D009154:Mutation; D010766:Phosphorylation; D010957:Plasmids; D013937:Thymidine Kinase / Q000235:genetics*
D000998:Antiviral Agents; D013937:Thymidine Kinase; D015774:Ganciclovir; D000212:Acyclovir