Biomarkers of dietary intake of micronutrients modulate DNA adduct levels in healthy adults.
DNA adducts, a reliable indicator of internal dose exposure to genotoxic agents and, possibly, of cancer risk, have been shown to be modulated by diet, particularly by the consumption of fresh fruit and vegetables, and by the intake of antioxidants (Palli et al., 2000, Int. J. Cancer, 87, 444-451). We have therefore investigated the association between DNA adducts in peripheral leukocytes and plasma levels of selected micronutrients, also taking into account the role of metabolic polymorphisms and smoking history, in a large independent random sample of volunteers enrolled in the prospective study EPIC-Italy (approximately 110 subjects from each of the three main geographical study areas, Northern, Central and Southern Italy). DNA adducts and five polymorphic metabolic genotypes were determined in peripheral leukocytes using the (32)P-post-labelling technique and PCR methods. Plasma levels of six carotenoids, retinol and alpha- and gamma-tocopherol were determined in the same blood sample. Among 331 subjects, 78.3% had detectable levels of DNA adducts (mean 7.46 +/- 0.48 per 10(9) nucleotides). Vitamin supplementation was reported by only a few subjects (3.9%). Strong inverse associations emerged between levels of DNA adducts and plasma retinol (P = 0.02), alpha-tocopherol (P = 0.04) and gamma-tocopherol (P = 0.03), but not carotenoids (except a borderline inverse association with beta-carotene, P = 0.08). An inverse significant association with plasma levels of retinol and gamma-tocopherol persisted in the subgroup of non-smokers, whereas a negative association with alpha-tocopherol emerged only in smokers. DNA adduct levels did not show any significant variation according to analyzed genotypes. Stratification by GSTM1 genotype, however, showed a significant negative association between DNA adduct levels and plasma levels of alpha- (P = 0.02) and beta-carotene (P = 0.02) in subjects with the GSTM1 null genotype. Our results confirm that biomarkers of dietary intake of antioxidants significantly modulate DNA adducts and suggest specific inverse associations between DNA adduct levels and antioxidant concentrations among GSTM1 null subjects and smokers.
Molecular and Nutritional Epidemiology Unit and Cancer Risk Factor Branch, Molecular Biology Laboratory - Cspo, Scientific Institute of Tuscany, Florence, Italy. d.palli@cspo.it
Domenico
D
Palli
Giovanna
G
Masala
Paolo
P
Vineis
Seymour
S
Garte
Calogero
C
Saieva
Vittorio
V
Krogh
Salvatore
S
Panico
Rosario
R
Tumino
Armelle
A
Munnia
Elio
E
Riboli
Marco
M
Peluso
D000328:Adult; D001483:Base Sequence; D015415:Biomarkers / Q000032:analysis*; D003430:Cross-Sectional Studies; D018736:DNA Adducts / Q000378:metabolism*; D017931:DNA Primers; D004032:Diet; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007558:Italy; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012016:Reference Values
D015415:Biomarkers; D018736:DNA Adducts; D017931:DNA Primers; D005982:Glutathione Transferase