Environmental Equity: A New Coalition for Justice

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 18mgKg-'dy-'; sulphasalazine 60mgKg-'dy-'; 5-aminosalicylic acid 30 and 60mgKg-'dy-' and olsalazine 60 mg Kg-' dy-' administered daily. Half of each group also received weekly injections of DMH 40mg Kg-'. Metronidazole, sulphasalazine and 30 mg Kg-' dy-' 5-aminosalicylic acid were co-carcinogenic, increasing either the number of cancers or tumour size. In contrast 60 mg Kg-' dy-' 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. An increased incidence of colonic cancer has long been known to be associated with inflammatory bowel disease, especially ulcerative colitis (Isabell & Levin, 1988). The causality of the association is now generally accepted. With ulcerative colitis, the known risk factors include the extent and the duration of the disease. The incidence is much higher, in those whose disease starts at a younger age and where there is total colonic involvement. It is now common clinical practice to use sulphasalazine and to a lesser extent, metronidazole for maintenance therapy in the treatment of chronic inflammatory bowel disease (Rosen et al., 1982). Could it be that these drugs influence the subsequent development of carcinoma? Using an accepted animal model (the production of colon cancer in rats using a chemical carcinogen, 1,2-dimethyl-hydrazine [DMH]), high dosage metronidazole has been shown to be co-carcinogenic (Sloan et al., 1983; A-Kareem et al., 1984). A number of published clinical case reports also implicate metronidazole in the production of colonic cancer (Krause et al., 1985). More recently, it has been postulated that sulphasalazine may play a role, in the subsequent development of colonic cancer in ulcerative colitis patients (Lashner et al., 1989). The constituents of sulphasalazine are sulphapyridine and 5-aminosalicylic acid (5-ASA). While sulphapyridine has no apparent beneficial effect in ulcerative colitis, it induces many of the side effects of sulphasalazine. In an earlier experiment we found that sulphapyridine had no effect on the size, or growth, of colonic carcinomas, in animals receiving DMH (unpublished data). The …