Experimental Tests of the Mutagenicity and Carcinogenicity of Nitric Oxide and Its Progenitors

Autor: L. M. Anderson, J. M. Rice, L.K. Keefer, C.M. Maragos, C.L. Driver, B. A. Diwan, D. C. Haines, David A. Wink
Rok vydání: 1995
Předmět:
Zdroj: Methods. 7:121-130
ISSN: 1046-2023
Popis: It is now well established that nitric oxide (NO) is both a critical bioregulatory agent essential to normal physiological function and a potentially toxic species. The primary goal of our NO research program is to investigate the possibility that exposure to NO might increase cancer risk. After reviewing some initial chemical and cella culture experiments from our laboratories suggesting that this might be the case, we report on two in vivo studies using standard carcinogenesis bioassay protocols of potential relevance. In one, application of nitroglycerin and two other NO-donor drugs at the maximum tolerated dose to the skin of SENECAR mice followed by promotion with 12-tetradecanoylphorbol-13-acetate failed to reveal any tumor-initiating activity. In the second, treatment of strain A mice with two other compounds containing the NO-releasing N2O−2 functional group (by gavage in adults and intraperitoneal injection neonates) increased lung adenoma incidence only when the NO donor producing a potenitally carcinogenic alkylating agent as a by-product was employed. We conclude that the practical significance of NO exposure in term of human cancer risk remains to be established.
Databáze: OpenAIRE