Effects of 1,4-phenylenebis(methylene)selenocyanate and selenomethionine on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced tumorigenesis in A/J mouse lung.
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.
Prokopczyk
B
B
American Health Foundation, Valhalla, NY 10595, USA.
Amin
S
S
Desai
D H
DH
Kurtzke
C
C
Upadhyaya
P
P
El-Bayoumy
K
K
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D008175:Lung Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D051379:Mice; D009602:Nitrosamines / Q000633:toxicity*; D016566:Organoselenium Compounds / Q000494:pharmacology*; D012645:Selenomethionine / Q000494:pharmacology*; D012907:Smoking / Q000009:adverse effects
D016588:Anticarcinogenic Agents; D009602:Nitrosamines; D016566:Organoselenium Compounds; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; C074153:1,4-phenylenebis(methylene)selenocyanate; D012645:Selenomethionine