Evaluation of the mutagenicity of the anti-inflammatory drug salicylazosulfapyridine (SASP).
Salicylazosulfapyridine, commonly known as sulfasalazine or SASP, is an anti-inflammatory drug that is widely used in the treatment of diseases such as ulcerative colitis and Crohn's disease. Increases in sister chromatid exchanges (SCE) and micronuclei (MN) frequencies have been reported in lymphocytes of patients maintained on SASP therapy for up to 21 months. We have tested SASP for its ability to induce chromosome aberrations (ABS) and SCE in cultured Chinese hamster ovary (CHO) cells, ABS in mouse bone marrow cells, and MN in erythrocytes from both bone marrow and peripheral blood of mice. In vitro assays for ABS and SCE were negative. In vivo, SASP administered by single gavage at doses up to 1000 mg/kg did not increase ABS in bone marrow cells of male B6C3F1 mice; however, increases in MN were observed in the peripheral blood erythrocytes of male and female B6C3F1 mice administered 675, 1350 or 2700 mg/kg SASP by gavage for 90 days. Weak but significant dose-related increases in MN were also observed in the bone marrow cells of male B6C3F1 mice administered 500, 1000 and 2000 mg/kg SASP for 3 days. These positive findings in mice support the role of SASP in the induction of MN and SCE in humans, and suggest the need for further evaluation of possible adverse human health effects associated with SASP therapy.
Bishop
J B
JB
National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Witt
K L
KL
Gulati
D K
DK
MacGregor
J T
JT
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D002460:Cell Line; D002869:Chromosome Aberrations; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015162:Micronucleus Tests; D009153:Mutagens; D012016:Reference Values; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D012460:Sulfasalazine / Q000494:pharmacology* / Q000633:toxicity
D009153:Mutagens; D012460:Sulfasalazine; D015127:9,10-Dimethyl-1,2-benzanthracene