In vitro induction of chromosome damage by sulphasalazine in human lymphocytes.
Two different endpoints, sister-chromatid exchange and micronucleus induction, were measured in human peripheral blood lymphocytes stimulated to divide in short-term in vitro cultures. The cultures were exposed to sulphasalazine and 6 of its metabolites for 72 h in the absence of any exogenous metabolic activation system. Analysis of the sister-chromatid exchange and micronuclei frequencies clearly indicates that sulphasalazine itself is capable of inducing both sister-chromatid exchange and micronuclei while sulphapyridine and its acetylated metabolites only induce sister-chromatid exchange. 5-Aminosalicylic acid, the therapeutic moiety of sulphasalazine, and its acetylated metabolite did not induce either sister-chromatid exchange or micronuclei at the concentrations tested. The data from these in vitro experiments are discussed in relation to the previously reported elevations in sister-chromatid exchange and micronucleus frequencies in inflammatory bowel disease patients receiving sulphasalazine therapy.
Mackay
J M
JM
Department of Genetics and Microbiology, Woodend Hospital, Aberdeen, Great Britain.
Fox
D P
DP
Brunt
P W
PW
Hawksworth
G M
GM
Brown
J E
JE
D002478:Cells, Cultured; D002877:Chromosomes, Human / Q000187:drug effects*; D006801:Humans; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects; D015162:Micronucleus Tests; D008940:Mitotic Index / Q000187:drug effects; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D012460:Sulfasalazine / Q000031:analogs & derivatives / Q000494:pharmacology*
D012460:Sulfasalazine