[Genotoxicity studies of cefmatilen hydrochloride hydrate (S-1090)].
Cefmatilen hydrochloride hydrate (S-1090), a new non-ester type of orally active cephem antibiotic synthesized in Shionogi Research Laboratories, was evaluated for its genotoxic potential using three assay systems. In a reverse mutation test with bacteria of Salmonella typhimurium TA100, TA1535, TA98, and TA1537, and Escherichia coli WP2uvrA using the preincubation method, the number of revertant colonies in the S-1090 treated plates was almost equal to that in the negative control plates in all strains with and without metabolic activation system with S9 mix (maximum dose, 100 micrograms/plate in TA98). In a chromosomal aberration test with cultured Chinese hamster lung cells (CHL/IU), S-1090 did not induce structural chromosome aberrations or polyploid cells either in the absence or presence of S9 mix up to the 50% growth inhibition doses. The potential of inducing clastogenicity and/or disruption of mitotic apparatus in vivo by S-1090 was evaluated by a micronucleus test with bone marrow cells of male Jc1:ICR mice. S-1090 suspended in 0.5% aqueous methylcellulose was administered by oral gavage up to 2000 mg/kg/day in single and double dosing groups. No induction of micronucleated polychromatic erythrocytes was observed 24 hr after the last dosing in each group. As all three genotoxicity tests showed negative responses, S-1090 is thought to have no genotoxic potential.
Kondo
K
K
Developmental Research Laboratories, Shionogi & Co., Ltd., 3-1-1 Futaba-cho, Toyonaka, Osaka 561-0825, Japan.
Takase
S
S
Nishimoto
Y
Y
Miyajima
H
H
Shiratori
O
O
Miyake
Y
Y
D000284:Administration, Oral; D000818:Animals; D002478:Cells, Cultured; D002511:Cephalosporins / Q000633:toxicity*; D002869:Chromosome Aberrations / Q000235:genetics; D006224:Cricetinae; D003412:Cricetulus; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D009153:Mutagens; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics
D002511:Cephalosporins; D009153:Mutagens; C419864:cefmatilen