Journal Article

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

Prashant Trikha, Nidhi Sharma and M. Athar

in Carcinogenesis

Volume 22, issue 8, pages 1207-1211
Published in print August 2001 | ISSN: 0143-3334
Published online August 2001 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/22.8.1207
Nitroglycerin: a NO donor inhibits TPA-mediated tumor promotion in murine skin

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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 ~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 tumorogenesis in murine skin.

Keywords: DMBA, 7,12-dimethylbenz[a]anthracene; GSH, reduced glutathione; GTN, nitroglycerin; NO, nitric oxide; ODC, ornithine decarboxylase; PMS, post-mitochondrial supernatant; TPA, 12-O-tetradecanoyl phorbol 13-acetate.

Journal Article.  4510 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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