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High Levels of DNA Adducts in Human Colon Are Associated with Colorectal Cancer¹

Ecole Nationale Supérieure Agronomique de Toulouse, Laboratoire de Toxicologie et Sécurité Alimentaire, 145 avenue de Muret, 31076 Toulouse [A. P-L., Y. G.]; Institut National de la Santé et de la Recherche Médicale U75, Centre Hospitalier Universitaire-Necker Enfants-Malades, Université René Descartes, 156 rue de Vaugirard, 75730 Paris Cedex 15 [V. C., P. B., I. d. W.]; Service de Chirurgie Digestive, Hôpital Laënnec, 42 rue de Sèvres. 75007 Paris [P-H. C., A. B.]; and Service d'Anatomo-pathologie, Hôpital Laënnec, 42 rue de Sèvres, 75007 Paris [F. C.], France

Colon cancer is one of the most frequent causes of cancer death in western countries. Epidemiological studies suggest that colorectal cancer can be attributed, at least in part, to carcinogens and mutagens present in the diet and/or the environment. The covalent binding of these xenobiotics or their reactive metabolities to DNA is believed to initiate this chemical carcinogenesis. In the present study, using a ³²P-postlabeling method, we investigated DNA adduct levels in control colons from patients without colorectal adenocarcinoma and in nontumoral and tumoral tissues from patients with colorectal adenocarcinoma. Our results show that the DNA adduct level is significantly higher (P < 0.001) in nontumoral than in control or tumoral colon samples. For the first time, we demonstrate in humans that the presence of numerous adducts in colonic mucosa is associated with colorectal cancer, a finding in agreement with the importance of chemical factors in causing this disease; therefore, after confirmation of the link between DNA adducts and colorectal cancer, the measurement of DNA adduct levels in colon samples could constitute a useful approach to the early detection of colorectal cancer.

¹ This work was supported by l'Institut National de la Santé et de la Recherche Médicale, l'Université René Descartes, la Ligue contre le Cancer Grant RS38, and l'Association pour la Recherche contre le Cancer Grant 66-04.

² To whom requests for reprints should be addressed, at INSERM U 75, CHU-Necker Enfants Malades, 156 rue de Vaugirard, 75730 Paris Cedex 15. France. Phone: 33 1 40 61 56 33; Fax: 33 1 40 61 55 82; E-mail: pbeaune@citi2.fr.

Received 7/20/95. Accepted 9/28/95.

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