Effect of vitamin levels on biomarkers of exposure and oxidative damage—The EXPAH study

P Farmer,B Binkova,C Ragin,I Kalina,R Singh,R.J Sram,T.A Popov,S Garte,E Taioli

doi:10.1016/j.mrgentox.2008.11.005

Abstract

DNA adducts are markers of carcinogen exposure and of their biological effect; they have been shown to be related to mutagenesis, and therefore they could be a predictive biomarker of human cancer. The objective of this study was to assess if there is a relationship between vitamins A, C, and E, which are known to play a significant role as free radical scavengers and antioxidant agents, and biomarkers of genotoxicity and oxidative stress. Three hundred and fifty-six subjects from Czech Republic, Slovak Republic and Bulgaria, who completed a questionnaire on dietary information and had a measurement of plasma A, C, E vitamins, DNA adduct levels (benzo[a]pyrene (B[a]P) and bulky (DNA-Tot) DNA adducts) and oxidative damage (cyclic pyrimidopurinone N-1,N2 malondialdehyde-2 deoxyguanosine (M1dG) and 8-oxo-7,8-dihydro-2_deoxyguanosine (8-oxodG)) were analyzed. A significant inverse correlation was observed between plasma vitamin levels and both benzo[a]pyrene (B[a]P) and bulky DNA adducts. Vitamin A was also significantly inversely correlated with M1dG, a marker of oxidative damage. The associations were stronger in non-smokers than in smokers. Dietary intake of certain antioxidants such as vitamins is associated with reduced levels of markers of DNA damage (B[a]P and DNA-Tot) and oxidation (M1dG and 8-oxodG) measured in peripheral white blood cells. This could contribute to the protective role of such a dietary pattern on cancer risk. The protective effect of dietary vitamins is less evident in smokers.

Highlights

Diet may be the source of several mutagens, such as aflatoxin and heterocyclic amines, whose biological effects on DNA have been studied extensively
Total DNA adducts were statistically inversely associated with vitamin C, A, E levels (Table 2); for vitamin E, the association was stronger in non smokers
There was no significant correlation between chromosomal aberrations by fluorescence in situ hybridization (FISH) and vitamin levels

Summary

Introduction

Diet may be the source of several mutagens, such as aflatoxin and heterocyclic amines, whose biological effects on DNA have been studied extensively. Other carcinogens present in diet, such as polycyclic aromatic hydrocarbons (PAH) and other aromatic compounds have been investigated less frequently. PAH may occur in fried and charcoal-grilled meat or in the food chain as a result of environmental pollution [1, 2]. PAHs are an important class of carcinogens, capable of inducing the formation of DNA adducts leading to DNA damage after metabolic activation [3]. This process may modify the long term individual cancer risk, at least with respect to lung cancer, as reported recently by a meta and pooled analysis [4]. The measure of genotoxicity in target organs such as lung, bladder and colon in relation to exposure seems to bring less convincing evidence [5]

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