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Felix, K.* ; Gerstmeier, S.* ; Kyriakopoulos, A.* ; Dong, H.-F. ; Eckhaus, M.* ; Behne, D.* ; Bornkamm, G.W. ; Janz, S.*

Selenium deficiency abrogates inflammation-dependent plasma cell tumors in mice.

Cancer Res. 64, 2910-2917 (2004)
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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 mug 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 mug of selenium/kg) and 15 of 40 (37.5%) control mice fed standard Purina chow (440 mug 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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords ELEVATED MUTANT FREQUENCIES; TRANSGENIC MOUSE MODEL; GLUTATHIONE-PEROXIDASE; BALB/C MICE; POLYMORPHONUCLEAR LEUKOCYTES; INDUCED PLASMACYTOMAGENESIS; THIOREDOXIN REDUCTASE; GENOME REARRANGEMENTS; CANCER PREVENTION; SPERM MATURATION
Language english
Publication Year 2004
HGF-reported in Year 0
ISSN (print) / ISBN 0008-5472
e-ISSN 1538-7445
Journal Cancer Research
Quellenangaben Volume: 64, Issue: 8, Pages: 2910-2917 Article Number: , Supplement: ,
Publisher American Association for Cancer Research (AACR)
Publishing Place Philadelphia, Pa.
Reviewing status Peer reviewed
Institute(s) Institute of Clinical Molecular Biology and Tumor Genetics (K.MOLBI)
POF-Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s) Immune Response and Infection
PSP Element(s) G-501400-006
DOI 10.1158/0008-5472.CAN-03-2672
Scopus ID 1942532136
Erfassungsdatum 2004-05-05
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