Selenium supplementation reduced oxidative DNA damage in adnexectomized BRCA1 mutations carriers.
Some experimental evidence suggests that BRCA1 plays a role in repair of oxidative DNA damage. Selenium has anticancer properties that are linked with protection against oxidative stress. To assess whether supplementation of BRCA1 mutation carriers with selenium have a beneficial effect concerning oxidative stress/DNA damage in the present double-blinded placebo control study, we determined 8-oxodG level in cellular DNA and urinary excretion of 8-oxodG and 8-oxoGua in the mutation carriers. We found that 8-oxodG level in leukocytes DNA is significantly higher in BRCA1 mutation carriers. In the distinct subpopulation of BRCA1 mutation carriers without symptoms of cancer who underwent adnexectomy and were supplemented with selenium, the level of 8-oxodG in DNA decreased significantly in comparison with the subgroup without supplementation. Simultaneously in the same group, an increase of urinary 8-oxoGua, the product of base excision repair (hOGG1 glycosylase), was observed. Therefore, it is likely that the selenium supplementation of the patients is responsible for the increase of BER enzymes activities, which in turn may result in reduction of oxidative DNA damage. Importantly, in a double-blinded placebo control prospective study, it was shown that in the same patient groups, reduction in cancer incidents was observed. Altogether, these results suggest that BRCA1 deficiency contributes to 8-oxodG accumulation in cellular DNA, which in turn may be a factor responsible for cancer development in women with mutations, and that the risk to developed breast cancer in BRCA1 mutation carriers may be reduced in selenium-supplemented patients who underwent adnexectomy.
Dziaman
Tomasz
T
Department of Clinical Biochemistry, Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland.
Huzarski
Tomasz
T
Gackowski
Daniel
D
Rozalski
Rafal
R
Siomek
Agnieszka
A
Szpila
Anna
A
Guz
Jolanta
J
Lubinski
Jan
J
Wasowicz
Wojciech
W
Roszkowski
Krzysztof
K
Olinski
Ryszard
R
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000291:Adnexal Diseases / Q000235:genetics / Q000601:surgery*; D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics / Q000601:surgery; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000187:drug effects; D009154:Mutation / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000097:blood / Q000235:genetics / Q000601:surgery; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D010919:Placebos; D011379:Prognosis; D018038:Sodium Selenite / Q000008:administration & dosage*; D014527:Uric Acid / Q000652:urine; D014815:Vitamins / Q000652:urine
D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D010919:Placebos; D014815:Vitamins; D014527:Uric Acid; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D018038:Sodium Selenite