Mouse skin ornithine decarboxylase induction and tumor promotion by cyclohexane.
Cyclohexane, a frequently used solvent in industry, was assessed for its tumorigenic potential on mouse skin following multistage initiation-promotion protocols. The activity of ornithine decarboxylase (ODC), a marker of tumor promotion was found to be induced by the topical application of cyclohexane. This ODC induction was dependent on the dose of cyclohexane used and the duration of application. Effect of protein synthesis inhibitors and the modifiers of tumor promotion on the cyclohexane induced ODC activity was also studied. ODC induction was inhibited by cycloheximide and also, up to some extent, by actinomycin D. Inhibitors of stage II tumor promotion showed more effect on the ODC induction by cyclohexane as compared to the inhibitors of stage I tumor promotion. In chronic animal bioassay experiments topical application of cyclohexane to DMBA initiated mouse skin resulted in just 10% of tumor bearing animals while prior application of TPA for two weeks resulted in 45% of tumor bearing animals. Collectively, the present study demonstrates that cyclohexane is more effective as a stage II tumor promoter over mouse skin and possibly affects the biochemical events at the molecular level.
Gupta
K P
KP
Laboratory of Environmental Carcinogenesis, Industrial Toxicology Research Centre, M.G. Marg, Lucknow, India.
Mehrotra
N K
NK
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D002273:Carcinogens; D003043:Cocarcinogenesis; D003510:Cyclohexanes / Q000037:antagonists & inhibitors / Q000633:toxicity*; D003513:Cycloheximide / Q000494:pharmacology; D004781:Environmental Exposure; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D051379:Mice; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D014176:Protein Biosynthesis; D012867:Skin / Q000187:drug effects* / Q000201:enzymology; D012878:Skin Neoplasms / Q000139:chemically induced; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity
D002273:Carcinogens; D003510:Cyclohexanes; D015127:9,10-Dimethyl-1,2-benzanthracene; D003513:Cycloheximide; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate