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Effects of basal level of antioxidants on oxidative DNA damage in humans

Marek Foksiński ,  Daniel Gackowski ,  Rafał Różalski ,  Jolanta Guz ,  Agnieszka B. Siomek ,  Tomasz Dziaman ,  Marek Jurgowiak ,  Ryszard S. Oliński 

Nicolaus Copernicus University, Collegium Medicum , Department of Clinical Biochemistry, ul. Karlowicza 24, Bydgoszcz 85-092, Poland

Abstract

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.

A relationship between basal level of antioxidants (vitamins A, C and E and uric acids) 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 analysed in healthy subjects (n=158).

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.

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 α-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. We have also found seasonal fluctuation of antioxidant vitamins and parameters which reflect DNA damage.

Our results suggest that oxidative DNA damage shows limited but significant response to antioxidants analysed in this study and is also affected by other cellular functions like antioxidant enzymes or DNA repair enzymes as well as genetics.

Acknowledgement

This work was supported in part by ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5: "Food Quality and Safety" (Contract No 513943).

 

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Presentation: Wykład at Zjazd Polskiego Towarzystwa Biochemicznego, Sympozjum M, by Marek Foksiński
See On-line Journal of Zjazd Polskiego Towarzystwa Biochemicznego

Submitted: 2007-05-08 15:51
Revised:   2009-06-07 00:44