Mutagenicity studies on catena-(S)-[mu-[N alpha-(3-aminopropionyl)histidinato(2-)-N1,N2,O:N tau]-zinc].
Z-103 (catena-(S)-[mu-[N alpha-(3-aminopropionyl)histidinato (2-)-N1,N2,O:N tau]-zinc], CAS 107667-60-7) was examined in the bacterial mutation test, a chromosomal aberration test with mammalian cells in culture and the micronucleus test using male mice. 1. Z-103 did not increase the number of revertants in Escherichia coli WP2 uvrA when tested at up to 5000 micrograms/plate in the presence or absence of metabolic activation. And Z-103 did not increase mutants in Salmonella typhimurium SD 100 (streptomycin dependent strain) or in Salmonella typhimurium TM677 (8-azaguanine sensitive strain) when tested at up to 5000 micrograms/ml in the presence or absence of metabolic activation. 2. The chromosomal aberration test was carried out with cultured Chinese hamster lung cells (CHL). For the direct assay procedure, the cells were treated with 3.3 x 10(-4)-3.3 x 10(-6) mol/l Z-103 for 24 or 48 h, after which time chromosome preparations were made. For the metabolic activation assay procedure, the cells were treated with 1.0 x 10(-3)-3.3 x 10(-6) mol/l of Z-103 for 6 h in the presence or absence of metabolic activation, and the chromosome preparations were made after a further 18-h incubation in the absence of Z-103 and metabolic activation. Z-103 did not cause chromosome aberrations either in the presence or in the absence of metabolic activation. 3. The micronucleus test was performed in ddY male mice. Z-103 was administered orally to mice at a dose of 400, 200 or 100 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)
Shibata
K
K
Department of Toxicology and Drug Metabolism, Zeria Pharmaceutical Co., Ltd., Saitama, Japan.
Matsuda
K
K
Ohta
T
T
Sasaki
Y
Y
Sutou
S
S
D000818:Animals; D000897:Anti-Ulcer Agents / Q000633:toxicity*; D001375:Azaguanine / Q000633:toxicity; D001419:Bacteria / Q000187:drug effects / Q000235:genetics; D001853:Bone Marrow / Q000648:ultrastructure; D002336:Carnosine / Q000031:analogs & derivatives*; D002869:Chromosome Aberrations; D006224:Cricetinae; D003412:Cricetulus; D004151:Dipeptides / Q000633:toxicity*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D066298:In Vitro Techniques; D051379:Mice; D008815:Mice, Inbred Strains; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009942:Organometallic Compounds / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013307:Streptomycin / Q000494:pharmacology; D017967:Zinc Compounds
D000897:Anti-Ulcer Agents; D004151:Dipeptides; D009153:Mutagens; D009942:Organometallic Compounds; D017967:Zinc Compounds; C061957:polaprezinc; D002336:Carnosine; D001375:Azaguanine; D013307:Streptomycin