High levels of DNA adducts in human colon are associated with colorectal cancer.

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 metabolites 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]  P. Beaune,et al.  Drug-metabolizing enzyme expression in human normal, peritumoral and tumoral colorectal tissue samples. , 1991, Carcinogenesis.

[2]  F. Kadlubar.  Detection of human DNA–carcinogen adducts , 1992, Nature.

[3]  Peter A. Jones,et al.  Progressing toward a molecular description of colorectal cancer development , 1992, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[4]  T. Sugimura,et al.  Carcinogenic factors in food with relevance to colon cancer development. , 1993, Mutation research.

[5]  F. Carbonell Tatay,et al.  [Primary tumors of the small intestine]. , 1989, Revista espanola de las enfermedades del aparato digestivo.

[6]  M A Butler,et al.  Rapid metabolic phenotypes for acetyltransferase and cytochrome P4501A2 and putative exposure to food-borne heterocyclic amines increase the risk for colorectal cancer or polyps. , 1994, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[7]  Mucosa-specific DNA adducts in human small intestine: a comparison with the colon. , 1994, Carcinogenesis.

[8]  F. Gonzalez,et al.  Role of human cytochromes P450 in the metabolic activation of chemical carcinogens and toxins. , 1994, Drug metabolism reviews.

[9]  B. Vogelstein,et al.  Prevalence of ras gene mutations in human colorectal cancers , 1987, Nature.

[10]  K. Bock.  Metabolic polymorphisms affecting activation of toxic and mutagenic arylamines. , 1992, Trends in pharmacological sciences.

[11]  P. Beaune,et al.  Comparison of mouse and human colon tumors with regard to phase I and phase II drug-metabolizing enzyme systems. , 1992, Cancer research.

[12]  M. V. Reddy,et al.  Nuclease P1-mediated enhancement of sensitivity of 32P-postlabeling test for structurally diverse DNA adducts. , 1986, Carcinogenesis.

[13]  S. Hirohashi,et al.  Multiple genetic alterations in human carcinogenesis. , 1992, Environmental health perspectives.

[14]  L. Vitetta,et al.  Alcohol consumption and the etiology of colorectal cancer: a review of the scientific evidence from 1957 to 1991. , 1992, Nutrition and cancer.

[15]  E C Miller,et al.  Searches for ultimate chemical carcinogens and their reactions with cellular macromolecules , 1981, Cancer.

[16]  F. Beland,et al.  DNA adduct measurements and tumor incidence during chronic carcinogen exposure in animal models: implications for DNA adduct-based human cancer risk assessment. , 1992, Chemical research in toxicology.

[17]  Y. Ohnishi,et al.  Presence of mucosa-specific DNA adduct in human colon: possible implication for colorectal cancer. , 1994, Carcinogenesis.

[18]  E. Creppy,et al.  DNA adduct formation in mice treated with ochratoxin A. , 1991, IARC scientific publications.

[19]  F. Beland,et al.  Formation and persistence of arylamine DNA adducts in vivo. , 1985, Environmental health perspectives.

[20]  W. Lutz,et al.  In vivo covalent binding of organic chemicals to DNA as a quantitative indicator in the process of chemical carcinogenesis. , 1979, Mutation research.

[21]  M. Lipkin,et al.  CELL PROLIFERATION KINETICS IN THE GASTROINTESTINAL TRACT OF MAN. I. CELL RENEWAL IN COLON AND RECTUM. , 1963, The Journal of clinical investigation.

[22]  Y. Grosse,et al.  Differential DNA adduct formation and disappearance in three mouse tissues after treatment with the mycotoxin ochratoxin A. , 1993, Mutation research.

[23]  J. Swenberg,et al.  Relationships between DNA adduct formation and carcinogenesis. , 1985, Environmental health perspectives.

[24]  N. van Zandwijk,et al.  Polycyclic aromatic hydrocarbon-DNA adducts in lung tissue from lung cancer patients. , 1990, Carcinogenesis.

[25]  D. Ledbetter,et al.  Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. , 1989, Science.