Effects of 1,4-phenylenebis(methylene)selenocyanate and selenomethionine on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced tumorigenesis in A/J mouse lung.

Abstract

We reported earlier that continuous feeding of 1,4-phenylenebis(methylene)selenocyanate (p-XSC) inhibited lung tumor induction by the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in the A/J mouse (El-Bayoumy et al., Carcinogenesis, 14, 1111-1113, 1993). The present investigation was designed to determine whether p-XSC inhibits pulmonary neoplasia induced by NNK in female A/J mice during the initiation phase of carcinogenesis or during the post-initiation phase. The naturally occurring selenomethionine was also included in this study. Doses higher than 4 p.p.m. of selenomethionine can induce toxic effects, therefore, dietary supplementation of this compound was selected at a dose level of 3.75 p.p.m. However, we were able to give p-XSC at selenium levels of 7.5 and 15 p.p.m., as mice can tolerate such doses in this form without any adverse effects. NNK was given by a single i.p. injection at dose of 10 micromol in 0.1 ml of saline. Selenomethionine did not show chemopreventive activity when administered in either phase of tumorigenesis. In contrast, p-XSC significantly reduced lung tumor multiplicity regardless of whether it was given during the initiation phase of tumorigenesis (P = 0.0009 at both levels of selenium) or post-initiation (P = 0.0009 at 15 p.p.m. and P = 0.036 for 7.5 p.p.m.). This is the first report describing that the synthetic organoselenium compound, p-XSC, can effectively block and suppress chemically (NNK)-induced lung tumor development in mice.

• Authors: B Prokopczyk, S Amin, D H Desai, C Kurtzke, P Upadhyaya, K El-Bayoumy
• Journal: Carcinogenesis (Carcinogenesis) Vol. 18 Issue 9 Pg. 1855-7 (Sep 1997) ISSN: 0143-3334 [Print] England
• PMID: 9328187 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anticarcinogenic Agents
• Nitrosamines
• Organoselenium Compounds
• 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone
• 1,4-phenylenebis(methylene)selenocyanate
• Selenomethionine

Topics

• Animals
• Anticarcinogenic Agents (pharmacology)
• Disease Models, Animal
• Female
• Lung Neoplasms (chemically induced, prevention & control)
• Mice
• Nitrosamines (toxicity)
• Organoselenium Compounds (pharmacology)
• Selenomethionine (pharmacology)
• Smoking (adverse effects)