Induction of chromosomal damage in mammalian cells in vitro and in vivo by sulfapyridine or 5-aminosalicylic acid.
Sulfapyridine (SP) and 5-aminosalicylic acid (5-ASA) are the two primary metabolites of the anti-inflammatory drug salicylazosulfapyridine (SASP). These two metabolites were studied for induction of chromosomal damage in mammalian cells, in vitro and in vivo, in an attempt to understand better the genetic effects produced by SASP in humans and laboratory mice. To this end, SP and 5-ASA were tested for induction of sister-chromatid exchanges (SCE) and chromosomal aberrations (Abs) in Chinese hamster ovary (CHO) cells in vitro. In addition, they were tested in vivo for induction of micronuclei (MN) in mouse bone marrow polychromatic erythrocytes (PCE). SP gave positive results in the in vitro SCE test and the in vivo MN test, and negative results in the in vitro Abs test. 5-ASA was negative in all three tests. These results indicate that it is the SP metabolite of SASP that is necessary for the induction of chromosomal damage reported to occur in humans and mice after treatment with SASP.
Witt
K L
KL
Oak Ridge Associated Universities, TN.
Bishop
J B
JB
McFee
A F
AF
Kumaroo
V
V
D000636:Aminosalicylic Acids / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D016466:CHO Cells; D002869:Chromosome Aberrations; D006224:Cricetinae; D015321:Gene Rearrangement / Q000187:drug effects; D008297:Male; D019804:Mesalamine; D051379:Mice; D008815:Mice, Inbred Strains; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D009153:Mutagens / Q000494:pharmacology* / Q000633:toxicity; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013427:Sulfapyridine / Q000494:pharmacology* / Q000633:toxicity
D000636:Aminosalicylic Acids; D009153:Mutagens; D019804:Mesalamine; D013427:Sulfapyridine