Use of an inducible hybrid viral gene as a model for evaluating drug effects on gene expression.
The glucocorticoid-inducible LTL gene [Cell 38:29-38 (1984)] was used as a model target to evaluate preferential drug effects on gene expression. Specifically, the potential of bleomycin, neocarzinostatin, and actinomycin D to induce alterations in either transcriptional or posttranscriptional gene expression was assessed. A Northern blot analysis was used to measure transcriptional effects, whereas changes in posttranscriptional expression were determined through an enzymatic assay for the thymidine kinase product of the LTL gene. Comparisons of the results from these assays with results obtained from assays that evaluated drug effects on cellular RNA and protein synthesis showed that none of the drugs were capable of inducing preferential effects on transcription. However, selective drug-induced effects on the expression of thymidine kinase activity were observed.
Beckmann
R P
RP
Grace Cancer Drug Center, Roswell Park Memorial Institute, Buffalo, New York 14263.
Beerman
T A
TA
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001761:Bleomycin / Q000494:pharmacology*; D015152:Blotting, Northern; D002460:Cell Line; D004274:DNA, Recombinant; D003609:Dactinomycin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D005814:Genes, Viral; D005938:Glucocorticoids / Q000494:pharmacology; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D009353:Zinostatin / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D004274:DNA, Recombinant; D005938:Glucocorticoids; D012333:RNA, Messenger; D001761:Bleomycin; D003609:Dactinomycin; D009353:Zinostatin; D013937:Thymidine Kinase