Nitroglycerin: a NO donor inhibits TPA-mediated tumor promotion in murine skin

Nitroglycerin (GTN), a nitric oxide (NO) generating vasodilator has been us ed 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 similar to 16-40% o f acetone-treated control. We also observed that GTN application led to a s ignificant reduction in the ornithine decarboxylase (ODC) activity and decr eased the rate of [H-3]thymidine incorporation into epidermal DNA when comp ared with the acetone-treated control (P < 0.001). Treatment of DMBA-initia ted 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 (tumo r/mouse) as compared with the TPA (alone)-treated group by 20 weeks. From t hese data, it can be concluded that NO can abrogate the toxic and tumor pro moting effects of TPA and GTN can be used as a chemopreventive agent to inh ibit tumorogenesis in murine skin.