Targeting of an inducible toxic phenotype in animal cells.
We have developed a toxic, or suicide, vector whose action is based on the targeted expression of the herpes simplex virus 1 thymidine kinase gene product in cultured cells or transgenic animals. This protein is able to convert nucleoside analogs such as acyclovir and 1-(2-deoxy-2-fluoro-beta-D-arabino-furanosyl)-5-iodouracil (FIAU) to toxic intermediates. The activation of these compounds disrupts cellular DNA replication, leading to rapid cell death. Neither acyclovir, FIAU, nor the herpes thymidine kinase alone is harmful to cells. This approach is simple and should have widespread applicability in studying lineage formation in cultured cells and transgenic animals.
Borrelli
E
E
Howard Hughes Medical Institute, Gene Expression Laboratory, Salk Institute, La Jolla, CA 92037.
Heyman
R
R
Hsi
M
M
Evans
R M
RM
D000212:Acyclovir / Q000633:toxicity*; D000818:Animals; D000998:Antiviral Agents / Q000633:toxicity*; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000633:toxicity; D015152:Blotting, Northern; D015139:Blotting, Southern; D002460:Cell Line; D002461:Cell Line, Transformed; D002470:Cell Survival; D004261:DNA Replication / Q000187:drug effects; D003720:Densitometry; D005786:Gene Expression Regulation; D051379:Mice; D008822:Mice, Transgenic; D010957:Plasmids / Q000187:drug effects; D051381:Rats; D018139:Simplexvirus / Q000187:drug effects / Q000201:enzymology; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013937:Thymidine Kinase / Q000235:genetics*; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology; D014162:Transfection; D014529:Uridine / Q000031:analogs & derivatives*
D000998:Antiviral Agents; D001086:Arabinofuranosyluracil; C043457:fialuridine; D013937:Thymidine Kinase; D014529:Uridine; D000212:Acyclovir