Effects of basal level of antioxidants on oxidative DNA damage in humans.
BACKGROUND
Vitamins A, E and C, and uric acid, which can scavenge free radicals should also protect DNA from the damage. It is reasonable to assume that agents that decrease oxidative DNA damage should also decrease subsequent cancer development.


OBJECTIVE
A relationship between basal level of antioxidants (vitamins A, C and E and uric acid) and oxidative DNA damage was assessed. For the first time, the broad spectrum of oxidative DNA damage biomarkers: urinary excretion of 8-oxodG, 8-oxoGua and 5HMUra as well as the level of oxidative DNA damage in leukocytes was analyzed in healthy subjects (n = 158).


METHODS
Using HPLC prepurification/isotope dilution GC/MS methodology, we examined the amount of oxidative DNA damage products excreted into urine and the amount of 8-oxodG in leukocytes' DNA (with HPLC/EC technique). The level of antioxidant vitamins and uric acid was estimated by HPLC technique with fluorimetric and UV detection.


RESULTS
Analyses of relationship between the most common antioxidants (vitamins A, C, E and uric acid) and oxidative DNA damage products reveal weak, statistically significant negative correlation between retinol and all the measured parameters except 5HMUra. Vitamin C negatively correlates with urinary excretion of 8-oxodG and 8-oxoGua. Uric acid revealed statistically significant negative correlation with 8-oxodG in cellular DNA and urinary excretion of 5HMUra, while alpha-tocopherol correlates negatively only with 8-oxodG in cellular DNA. Good, significant (P < 0.0001), positive correlation (r = 0.61) was noted between urinary levels of the base, 8-oxoGua and the deoxynucleoside, 8-oxodG.


CONCLUSIONS
Our results suggest that oxidative DNA damage shows limited but significant response to antioxidants analyzed in this study and is more affected by many other cellular functions like antioxidant enzymes or DNA repair enzymes as well as genetics.
Foksinski
Marek
M
Department of Clinical Biochemistry, Collegium Medicum Nicolaus Copernicus University, Karlowicza 24, 85-092 Bydgoszcz, Poland.
Gackowski
Daniel
D
Rozalski
Rafal
R
Siomek
Agnieszka
A
Guz
Jolanta
J
Szpila
Anna
A
Dziaman
Tomasz
T
Olinski
Ryszard
R
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000008:administration & dosage / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D005260:Female; D016166:Free Radical Scavengers; D006147:Guanine / Q000031:analogs & derivatives / Q000652:urine; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology / Q000209:etiology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D014527:Uric Acid / Q000008:administration & dosage / Q000378:metabolism*; D014815:Vitamins / Q000008:administration & dosage / Q000378:metabolism*
D000975:Antioxidants; D015415:Biomarkers; D016166:Free Radical Scavengers; D014815:Vitamins; D014527:Uric Acid; C024829:8-hydroxyguanine; D006147:Guanine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine