Toenail selenium status and DNA repair capacity among female BRCA1 mutation carriers.
Selenium is an important cofactor of various antioxidant enzymes and has been shown to enhance DNA repair in normal human fibroblasts. Oral selenium supplementation has also been shown to decrease the number of chromosome breaks in BRCA1 mutation carriers. Because the predisposition to cancer among BRCA1 mutation carriers may be linked to high rates of DNA damage and chromosome breakage, we evaluated the association between toenail selenium concentrations and three measures of DNA repair capacity (the single-cell alkaline gel electrophoresis (comet) assay, the micronucleus test, and the enumeration of gamma-H2AX nuclear foci) in female BRCA1 mutation carriers and in non-carriers. Toenail selenium levels were inversely associated with levels of chromosomal damage following exposure to gamma-irradiation, as assessed by the micronucleus test. This association was limited to women with a BRCA1 mutation (p = 0.03). Toenail selenium was not a significant predictor of DNA repair capacity, as quantified by either the comet assay or the number of gamma-H2AX foci, in carriers or in non-carriers. These results provide evidence for a possible protective effect of selenium against BRCA1-associated breast cancers.
Kotsopoulos
Joanne
J
Women's College Research Institute, 790 Bay Street, Toronto, Ontario, Canada. joanne.kotsopoulos@wchospital.ca
Chen
Zhou
Z
Vallis
Katherine A
KA
Poll
Aletta
A
Ghadirian
Parviz
P
Kennedy
Greg
G
Ainsworth
Peter
P
Narod
Steven A
SA
D000328:Adult; D016022:Case-Control Studies; D020552:Comet Assay; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D006579:Heterozygote; D006657:Histones / Q000032:analysis; D006801:Humans; D015162:Micronucleus Tests; D008875:Middle Aged; D009154:Mutation; D009262:Nails / Q000737:chemistry*; D012643:Selenium / Q000032:analysis*
C468783:H2AX protein, human; D006657:Histones; D012643:Selenium