Nitroglycerin: a NO donor inhibits TPA-mediated tumor promotion in murine skin.
Nitroglycerin (GTN), a nitric oxide (NO) generating vasodilator has been used in the present study to assess the role of NO during tumor promotion in murine skin. Administration of GTN to 12-O tetradecanoyl phorbol 13-acetate (TPA)-treated mice resulted in a dose-dependent inhibition in the level of glutathione and the activity of antioxidant enzymes by approximately 16-40% of acetone-treated control. We also observed that GTN application led to a significant reduction in the ornithine decarboxylase (ODC) activity and decreased the rate of [3H]thymidine incorporation into epidermal DNA when compared with the acetone-treated control (P < 0.001). Treatment of DMBA-initiated TPA-promoted mice with GTN increased the latency period, decreased the tumor incidence by 32% and there was a 2-fold decrease in tumor yield (tumor/mouse) as compared with the TPA (alone)-treated group by 20 weeks. From these data, it can be concluded that NO can abrogate the toxic and tumor promoting effects of TPA and GTN can be used as a chemopreventive agent to inhibit tumorigenesis in murine skin.
Trikha
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P
Department of Medical Elementology and Toxicology, Hamdard University, Hamdard Nagar, New Delhi 110 062, India. prashant_trikha@hotmail.com
Sharma
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N
Athar
M
M
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D051379:Mice; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D005996:Nitroglycerin / Q000494:pharmacology*; D010212:Papilloma / Q000139:chemically induced / Q000517:prevention & control*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D002273:Carcinogens; D020030:Nitric Oxide Donors; D005996:Nitroglycerin; D013755:Tetradecanoylphorbol Acetate