Detection of malondialdehyde DNA adducts in human colorectal mucosa: relationship with diet and the presence of adenomas.
Colorectal biopsies from normal mucosa of participants in the United Kingdom Flexible Sigmoidoscopy Trial and European Prospective Investigation on Cancer (EPIC; n = 162) were analyzed for the presence of malondialdehyde-deoxyguanosine (M(1)-dG), a DNA adduct derived from lipid peroxidation. The aim was to investigate whether dietary factors can modulate M(1)-dG levels and whether M(1)-dG in normal mucosa is a risk factor for colorectal adenomas. Samples were analyzed using a sensitive immunoblot blot assay. This study has shown for the first time that M(1)-dG is present in human colorectal tissue. M(1)-dG levels ranged from undetectable (n = 13) to 12.23 per 10(7) total bases. Mean levels were 4.3 +/- 3 and 4.6 +/- 2.9 per 10(7) total bases in men and women, respectively. In men, there were positive associations of adduct levels with height and age, and inverse associations with body mass index. Legumes, fruit, salad, and whole meal bread were inversely associated with M(1)-dG adducts, whereas consumption of offal, white meat, beer, and alcohol were positively associated with elevated levels. In women, there was an inverse association of the adduct with the ratio of polyunsaturated:saturated fatty acids (P = 0.019) and a weak positive correlation with saturated fat (P < 0.061). When levels of adducts were compared in individuals with and without adenomas, there was a trend for higher levels in individuals presenting with adenomas especially in the highest category of M(1)-dG adducts (P < 0.005).
Leuratti
Chiara
C
Medical Research Council Toxicology Unit, University of Leicester, Leicester LE1 9HN, United Kingdom. chiara_leuratti@hotmail.com
Watson
Mark A
MA
Deag
Eliot J
EJ
Welch
Ailsa
A
Singh
Rajinder
R
Gottschalg
Elke
E
Marnett
Lawrence J
LJ
Atkin
Wendy
W
Day
Nicholas E
NE
Shuker
David E G
DE
Bingham
Sheila A
SA
D000236:Adenoma / Q000737:chemistry / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000032:analysis*; D003106:Colon; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000235:genetics*; D018736:DNA Adducts / Q000032:analysis*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis*; D005247:Feeding Behavior; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007413:Intestinal Mucosa / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012007:Rectum; D012307:Risk Factors
D014408:Biomarkers, Tumor; D018736:DNA Adducts; C089188:3-(2'-deoxyribofuranosyl)pyrimido(1,2-a)purin-10(3H)-one; D003849:Deoxyguanosine