The effect of therapeutic drugs used in inflammatory bowel disease on the incidence and growth of colonic cancer in the dimethylhydrazine rat model.
An increased incidence of colonic cancer is associated with chronic inflammatory bowel disease. Sulphasalazine, metronidazole and more recently, modified forms of 5-aminosalicylic acid are used for maintenance therapy of inflammatory bowel disease. In a series of experiments, we used the 1,2-dimethylhydrazine animal model of colonic cancer in conjunction with these drugs, to study the effect on the development of colon cancer. Inbred male Wistar rats were divided into groups receiving orally: metronidazole 18 mg Kg-1 dy-1; sulphasalazine 60 mg Kg-1 dy-1; 5-aminosalicylic acid 30 and 60 mg Kg-1 dy-1 and olsalazine 60 mg Kg-1 dy-1 administered daily. Half of each group also received weekly injections of DMH 40 mg Kg-1. Metronidazole, sulphasalazine and 30 mg Kg-1 dy-1 5-aminosalicylic acid were co-carcinogenic, increasing either the number of cancers or tumour size. In contrast 60 mg Kg-1 dy-1 5-aminosalicylic acid inhibited tumour size and olsalazine had no effect. These results may have a bearing on long term maintenance therapy in inflammatory bowel disease.
Department of Gastroenterology, Prince of Wales Hospital, Randwick, NSW, Australia.
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Davis
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Patterson
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Crouch
D000230:Adenocarcinoma / Q000139:chemically induced* / Q000209:etiology / Q000473:pathology; D000636:Aminosalicylic Acids / Q000009:adverse effects*; D000818:Animals; D003043:Cocarcinogenesis; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000209:etiology / Q000473:pathology; D004127:Dimethylhydrazines; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004357:Drug Synergism; D015994:Incidence; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000188:drug therapy*; D008297:Male; D019804:Mesalamine; D008795:Metronidazole / Q000009:adverse effects*; D009361:Neoplasm Invasiveness; D051381:Rats; D017208:Rats, Wistar; D012460:Sulfasalazine / Q000009:adverse effects*
D000636:Aminosalicylic Acids; D004127:Dimethylhydrazines; D008795:Metronidazole; D012460:Sulfasalazine; D019804:Mesalamine; C032587:olsalazine