期刊
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
卷 19, 期 6, 页码 396-405出版社
WILEY
DOI: 10.1002/jbt.20105
关键词
selenium; selenocysteine; selenazolidines; prodrugs; cancer chemoprevention
资金
- NATIONAL CANCER INSTITUTE [P30CA042014] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [S10RR014768, S10RR006262] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM058913] Funding Source: NIH RePORTER
- NCI NIH HHS [P30 CA42014] Funding Source: Medline
- NCRR NIH HHS [S10 RR14768, RR06262] Funding Source: Medline
- NIGMS NIH HHS [R01 GM58913] Funding Source: Medline
Prodrugs of L-selenocysteine have potential utility in cancer chemoprevention. This study reports the efficacy of three selenazolidine-4(R)carboxylic acids, (2-unsubstituted, 2-oxo, and 2-methyl derivatives; SCA, OSCA, and MSCA, respectively) against tobacco-related lung tumorigenesis in a mouse model. Seven days after initiation of an AIN-76A diet supplemented with sodium selenite (5 ppm Se), I.-selenomethionine (3.75 ppm Se), Se-methyl-L-selenocysteine (3 ppm Se), L-selenocystine (15 ppm Se), SCA (15 ppm Se), OSCA (15 ppm Se), or MSCA (15 ppm Se), mice received 4-(methylnitrosamino)-1(3-pyridyl)-1-butanone (NNK; 10 mu mol, i.p.). After an additional 16 weeks on the diets, two compounds, OSCA and selenocystine, significantly reduced lung adenoma multiplicity from 7.2 tumors per mouse in the NNK group to 4.5 and 4.6 tumors per mouse, respectively. Neither selenium concentration nor glutathione peroxidase activity in either RBCs or liver served as surrogate indicators of tumor reduction. Hepatic selenium levels were significantly elevated by all selenium-containing compounds except Se-methyl-L-selenocysteine and SCA; RBC selenium levels by all except sodium selenite and MSCA. With the exception of L-selenomethionine, RBC glutathione peroxidase activity was increased along with the elevated selenium levels. Hepatic glutathione peroxidase activity was elevated by all Se-compounds except SCA. The two compounds showing significant tumor reduction (OSCA and selenocystine) were the only two compounds that showed ubiquity of changes, elevating both selenium levels and GPx activity in both liver and RBC. (c) 2005 Wiley Periodicals, Inc.
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