Inflammatory bowel disease and sulphasalazine therapy : a cytogenetic study
Ulcerative colitis and Crohn's colitis are chronic inflammatory bowel diseases that occur with a high frequency in the North-East of Scotland. They are diseases of adolescents and young adults, although they may have their onset at any age. The aetiology is largely unknown. Oral sulphasalazine is used as the treatment of choice for the prevention of relapses. At present there is no satisfactory alternative and so, on present practice, patients may take the drug indefinitely after diagnosis of the disease. Inflammatory bowel disease itself does not increase the levels of sister chromatid exchange and micronuclei observed in the lymphocytes of the patients. Patients receiving sulphasalazine therapy, however, have significantly elevated levels of sister chromatid exchange and micronuclei in their lymphocytes compared to control individuals. In addition, patients show a significant elevation in sister chromatid exchange and micronuclei frequencies after commencing sulphasalazine therapy. The length of time on sulphasalazine is influential in determining the sister chromatid exchange frequency as is the acetylator phenotype of the patient. Sister chromatid exchange frequencies appear to remain elevated for many months after cessation of therapy, suggesting that the lesions produced by the sulphasalzine therapy are long-lived. In vitro studies have shown that sulphasalazine induces both sister chromatid exchange and micronuclei in human lymphocytes, whereas sulphapyridine and its acetylated metabolites induce only sister chromatid exchanges. 5-aminosalicylic acid, the active moiety of sulphasalazine, and its acetylated metabolite do not induce sister chromatid exchange or micronuclei at the concentrations tested. The present and future use of sulphasalazine therapy should be evaluated in light of these results, and the use of new drugs, based on the 5-aminosalicylic moiety should be encouraged to reduce the potential genetic risk to the patients.