Selenium deficiency abrogates inflammation-dependent plasma cell tumors in mice. Cancer Res 2004 Apr 15;64(8):2910-7
Date
04/17/2004Pubmed ID
15087411DOI
10.1158/0008-5472.can-03-2672Scopus ID
2-s2.0-1942532136 (requires institutional sign-in at Scopus site) 31 CitationsAbstract
The role of the micronutrient, selenium, in human cancers associated with chronic inflammations and persistent infections is poorly understood. Peritoneal plasmacytomas (PCTs) in strain BALB/c (C), the premier experimental model of inflammation-dependent plasma cell transformation in mice, may afford an opportunity to gain additional insights into the significance of selenium in neoplastic development. Here, we report that selenium-depleted C mice (n = 32) maintained on a torula-based low-selenium diet (5-8 micro g of selenium/kg) were totally refractory to pristane induction of PCT. In contrast, 11 of 26 (42.3%) control mice maintained on a selenium adequate torula diet (300 micro g of selenium/kg) and 15 of 40 (37.5%) control mice fed standard Purina chow (440 micro g of selenium/kg) developed PCT by 275 days postpristane. Abrogation of PCT was caused in part by the striking inhibition of the formation of the inflammatory tissue in which PCT develop (pristane granuloma). This was associated with the reduced responsiveness of selenium-deficient inflammatory cells (monocytes and neutrophils) to chemoattractants, such as thioredoxin and chemokines. Selenium-deficient C mice exhibited little evidence of disturbed redox homeostasis and increased mutant frequency of a transgenic lacZ reporter gene in vivo. These findings implicate selenium, via the selenoproteins, in the promotion of inflammation-induced PCT and suggest that small drug inhibitors of selenoproteins might be useful for preventing human cancers linked with chronic inflammations and persistent infections.
Author List
Felix K, Gerstmeier S, Kyriakopoulos A, Howard OM, Dong HF, Eckhaus M, Behne D, Bornkamm GW, Janz SAuthor
Siegfried Janz MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsChemotaxis
Diet
Inflammation
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Transgenic
Mutation
Oxidation-Reduction
Peritoneal Neoplasms
Plasmacytoma
Selenium
Terpenes
Tissue Distribution
