Summary
Epidemiologic considerations, geographic pathology, and migrant studies definitely indicate that cancer in the gastrointestinal tract, in particular in the stomach and in the colon is mediated by environmental factors, especially dietary components. In recent years specific chemicals which induce cancer of the colon in animal systems have been discovered. Thus, model experiments are currently being performed to study the actions of environmental factors on the effectiveness of such chemicals in leading to colorectal cancer. Thus, hopefully, these experiments will pinpoint those agents in the environment which exert a controlling influence in this disease. Information on the metabolism of the chemical carcinogens affecting the lower gut indicates that certain of the metabolic steps may be performed in the liver, after which active metabolites are secreted in the bile in a protected conjugated form. The key ultimate carcinogen is then released in the colon by enzymes produced by bacterial microflora. A number of alternative pathways can also develop active carcinogens by microbial action in the gut, or by metabolic activation mediated by enzyme systems in colonic epithelium. Thus, studies of the effects of environmental agents in modifying flora in the lumens of specific enzyme systems in the intestinal wall are important in understanding the complex problems related to the etiology of colonic cancer.
Similar content being viewed by others
References
American Cancer Society: Cancer Facts and Figures. New York, The Society, 1972
Bollag W: Vitamin A and vitamin A acid in the prophylaxis and therapy of epithelial tumours. Int Z Vitaminforsch 40: 299, 1970
Burkitt DP: Epidemiology of cancer of the colon and rectum. Cancer 28: 3, 1971
Cleaver JE: Xeroderma pigmentosum: Variants with normal DNA repair and normal sensitivity to ultraviolet light. J Invest Dermatol 58: 124, 1972
Cole JW: Quoted by Wynder EL, Kajitani T, Dodo H. et al: Environmental factors of cancer of the colon and rectum. II. Japanese epidemiological data. Cancer 23: 1210, 1969
Cutler SJ: Trends in cancers of the digestive tract. Surgery 65: 740, 1969
Di Luzio NR: Protective effect of vitamin E on plasma lipid dienes in man. J Agric Food Chem 20: 486, 1972
Druckrey H: Production of colonic carcinomas by 1,2-dialkylhydrazines and azoxyalkanes, Carcinoma of the Colon and Antecedent Epithelium. Edited by WJ Burdette. Springfield, Ill., Charles C Thomas, 1970, chapter 20, p 267
Fortner JG: Tumors of the alimentary tract in the hamster and cat, Carcinoma of the Alimentary Tract: Etiology and Pathogenesis. Edited by WJ Burdette. Salt Lake City, University of Utah Press, 1965, p 75
Gennaro AR, Villanueva R, Sukonthaman Y, et al.: Chemical carcinogenesis in transposed intestinal segments. Cancer Res 33: 536, 1973
Gold P: Quoted by Hellström I, Hellström KE: Newer concepts of cancer of the colon and rectum: Cellular immunity to human colonic carcinomas. Dis Colon Rectum 15: 100, 1972
Haenel H: Human normal and abnormal gastrointestinal flora. Am J Clin Nutr 23: 1433, 1970
Haenszel WM, Correa P: Cancer of the colon and rectum and adenomatous polyps: A review of epidemiologic findings. Cancer 28: 14, 1971
Herrold KM: Adenocarcinomas of the intestine induced in Syrian hamsters by N-methyl-N-nitrosourea. Pathol Vet 6: 403, 1969
Hill MJ, Aries VC: Faecal steroid composition and its relationship to cancer of the large bowel. J Pathol 104: 129, 1971
Hill MJ, Drasar BS, Hawksworth G, et al: Bacteria and aetiology of cancer of large bowel. Lancet 1: 95, 1971
Kayden HJ, Nair PP: Vitaman E and its role in cellular metabolism. NY Acad Sci, December 6–7, 1971
Kent TH, Fischer LJ, Marr R: Glucuronidase activity in intestinal contents of rat and man and relationship to bacterial flora. Proc Soc Exp Biol Med 140: 590, 1972
Laqueur GL: Contribution of intestinal macroflora and microflora to carcinogenesis. Carcinoma of the Colon and Antecedent Epithelium. Edited by WJ Burdette. Springfield, Ill., Charles C Thomas, 1970, chapter 24, p 305
Laqueur GL, Spatz M: Toxicology of cycasin. Cancer Res 28: 2262, 1968
Leaver DD, Swann PF, Magee PN: The induction of tumours in the rat by a single oral dose of N-nitrosomethylurea. Br J Cancer 23: 177, 1969
Lipkin M, Deschner E, Troncale F: Cell differentiation and the development of colonic neoplasma. Gastroenterology 59: 303, 1970
Lutton C, Chevallier F: Analyse des sterols des contenus digestifs et des feces du rat. Biochem Biophys Acta 260: 133, 1972
Marjanen H: Possible causal relationship between the easily soluble amount of manganese on arable mineral soil and susceptibility to cancer in Finland. Ann Agric Fenniae 8: 326, 1969
Mirvish SS: Kinetics of nitrosamide formation from alkylureas, N-alkylurethans and alkylguanidines: Possible implications for the etiology of human gastric cancer. J Natl Cancer Inst 46: 1183, 1971
Montesano R, Magee PN: Evidence of formation of N-methyl-N-nitrosourea in rats given N-methylurea and sodium nitrite. Int J Cancer 7: 249, 1971
Morson BC, Bussey HJ: Predisposing causes of intestinal cancer, Current Problems in Surgery. Edited by MM Ravitch. Chicago, Year Book Medical Publishers, Inc., February 1970, 50 pp
Murray JF (editor): Symposium on Tumors of the Alimentary Tract in Africans. NCI monograph number 25, 1967
Narisawa T, Sato T, Hayakawa M, et al: Carcinoma of the colon and rectum of rats by rectal infusion of N-methyl-N′-nitro-N-nitrosoguanidine. Gann 62: 231, 1971
Nigro ND, Bhadrachari N, Chomchai C: A rat model for studying colonic cancer: Effect of cholestyramine on induced tumors. Dis Colon Rectum 16: 438, 1973
Rose EF: The effects of soil and diet on disease. Cancer Res 28: 2390, 1968
Sander J, Bürkle G, Flohe L, et al: Untersuchungen in vitro über die Möglichkeit einer Bildung cancerogener Nitrosamide im Magen. Arzneim Forsch 21: 411, 1971
Schoental R, Bensted JP: Tumors of the intestines induced in rats by intraperitoneal injections of N-methyl- and N-ethyl-N-nitrosourethanes. Br J Cancer 22: 316, 1968
So BT, Magadia NE, Wynder EL: Induction of carcinomas of the colon and rectum in rats by intrarectal injections of N-methyl-N-nitro-N-nitrosoguanidine. J Natl Cancer Inst 50: 927, 1973
So BT, Wynder EL: Induction of hamster tumors of the urinary bladder by 3,2′-dimethyl-4-aminobiphenyl. J Natl Cancer Inst 48: 1733, 1972
Spatz M: Carcinogenicity of methylazoxymethanol (MAM) in guinea pigs and hamsters. Abstracts 10th Internat. Cancer Congress. Houston, 1970, p 24
Speck RS, Calloway DH, Hadley WK: Human fecal flora under controlled diet intake. Am J Clin Nutr 23: 1488, 1970
Spjut HJ: Newer concepts of cancer of the colon and rectum: Similarities between human and experimentally induced tumors of the large intestine. Dis Colon Rectum 15: 94, 1972
Visek WJ: Effects of urea hydrolysis on cell life-span and metabolism. Fed Proc 31: 1178, 1972
Walpole AL, Williams MH: Aromatic amines as carcinogens in industry. Br Med Bull 14: 141, 1958
Wattenberg LW: Studies of polycyclic hydrocarbon hydroxylases of the intestine possibly related to cancer: Effect of diet on benzpyrene hydroxylase activity. Cancer 28: 99, 1971
Weisburger JH: Colon carcinogens: Their metabolism and mode of action. Cancer 28: 60, 1971
Weisburger JH: Chemical carcinogenesis, Cancer Medicine, Edited by JF Holland, E Frei. Philadelphia, Lea and Febiger, 1973
Weisburger JH, Weisburger EK: Biochemical formation and pharmacological, toxicological and pathological properties of hydroxylamines and hydroxamic acids. Pharmacol Rev 25: 1, 1973
Williams JR Jr, Grantham PH, Marsh HH III, et al: Participation of liver fractions and of intestinal bacteria in the metabolism of N-hydroxy-N-2-fluorenylacetamide in the rat. Biochem Pharmacol 19: 173, 1970
Winitz M, Adams RF, Seedman DA, et al: Studies in metabolic nutrition employing chemically defined diets. II. Effect on gut microflora populations. Am J Clin Nutr 23: 546, 1970
Wittig G, Wildner GP, Ziebarth D: Der Einfluss der Ingesta auf die Kanzerisierung des Rattendarms durch Dimethylhydrazin. Arch Geschwulstforsch 37: 105, 1971
Wynder EL, Shigematsu T: Environmental factors of cancer of the colon and rectum. Cancer 20: 1520, 1967
Author information
Authors and Affiliations
Additional information
Read at the meeting of the American Proctologic Society, New York, New York, June 11 to 14, 1972.
About this article
Cite this article
Weisburger, J.H. Chemical carcinogens and their mode of action in colonic neoplasia. Dis Colon Rectum 16, 431–437 (1973). https://doi.org/10.1007/BF02588865
Issue Date:
DOI: https://doi.org/10.1007/BF02588865