Induction of thymidine kinase in mouse skin exposed to 12-O-tetradecanoylphorbol-13-acetate.
Topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) exhibited an increase in the epidermal thymidine kinase (TK) activity in a dose dependent manner. Maximum induction of TK was observed at a TPA concentration of 2.5 microg per animal. The induction of TK by TPA appeared to be a function of time with the maximum TK induction between 4 and 16 h after TPA application. Repeated applications of TPA every 24 h did not show any cumulative effect rather TK activity appeared to be normal after two applications. However, repeated applications of TPA at an interval of 48 h exhibited increased TK activity even after 16 applications. Cycloheximide and actinomycin D, the inhibitors of protein and RNA synthesis, inhibited the TPA induced activation of TK. Our results demonstrated that TPA induced the TK activity may be, by increasing de novo synthesis of enzyme protein and this induction might lead to increased de novo DNA synthesis after TPA application. DMBA was used as a reference compound. As far as the authors are aware, this is the first report on TK induction by topical application of TPA.
Gupta
K P
KP
Environmental Carcinogenesis Division, Industrial Toxicology Research Centre, Post Box No. 80, Mahatma Gandhi Marg, 226 001, Lucknow, India. intox@itrc.sirnetd.ernet.in
Rani
R
R
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D051379:Mice; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012867:Skin / Q000187:drug effects / Q000201:enzymology*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*; D013937:Thymidine Kinase / Q000096:biosynthesis*; D013997:Time Factors
D002273:Carcinogens; D019384:Nucleic Acid Synthesis Inhibitors; D011500:Protein Synthesis Inhibitors; D015127:9,10-Dimethyl-1,2-benzanthracene; D013937:Thymidine Kinase; D013755:Tetradecanoylphorbol Acetate