DNA adducts in normal colonic mucosa from healthy controls and patients with colon polyps and colorectal carcinomas.
Colon cancer is a multistage process where adenomatous polyps developing in a normal mucosa may further progress to neoplasia. DNA adducts are biomarkers linked to exposure to carcinogenic compounds, tumour formation and clinically observed cancer. Such DNA adducts have been detected in the mucosa of colon cancer patients. The aim of this study was to investigate whether there are differences in DNA adduct levels and patterns in mucosa from patients with colon cancer, polyps and non-cancerous controls and whether some DNA adducts could be markers for colon cancer development. Human colonic biopsies were collected from healthy controls (n = 10), polyp patients (n = 22) (from both normal and polyp tissue) and colon cancer patients (n = 32) (from both tumour tissue and adjacent normal mucosa). In 150 tissues specimens (when small amount of tissue, the same type of tissues were pooled from each patient), DNA adduct levels and patterns were analysed by the (32)P-high-performance liquid chromatography method. There were no significant difference in the total levels of DNA adducts between any of the groups. Levels of two single DNA adducts were decreased in mucosa adjacent to tumours as compared to mucosa from healthy controls. One DNA adduct was found only in tumour tissue and adjacent mucosa from the colon cancer patients. A food derived, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-related DNA adduct was detected in 106 of the 150 tissues analysed, but in similar levels in tissues from controls, polyp patients or cancer patients. In conclusion, three individual DNA adducts may be interesting candidates for further evaluation of their possible role as biomarkers in human carcinogenesis. Furthermore, a food-derived PhIP-related adduct contributes to the general DNA adduct pattern in most individuals, indicating a minor role of this adduct in human colon carcinogenesis.
Jonsson
Charlotte
C
Department of Biosciences, Laboratory for Analytical Toxicology, Novum Research Park, Karolinska Institutet, SE-141 83 Huddinge, Sweden.
Stål
Per
P
Sjöqvist
Urban
U
Akerlund
Jan-Erik
JE
Löfberg
Robert
R
Möller
Lennart
L
D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D003111:Colonic Polyps / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D018736:DNA Adducts / Q000378:metabolism*; D006262:Health; D006801:Humans; D007093:Imidazoles / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D012015:Reference Standards
C502239:2-amino-1-methyl-6-phenolimidazo(4,5-b)pyridine-DNA adduct; D018736:DNA Adducts; D007093:Imidazoles