Mutagenicity Studies of (+)-Monocalcium bis[(3R,5S,6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]-3,5-dihydroxy-6-heptenoate] (NK-104).
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Accession number;99A0540722
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| Title;Mutagenicity Studies of (+)-Monocalcium bis[(3R,5S,6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]-3,5-dihydroxy-6-heptenoate] (NK-104). |
| Author;
OKAMURA NOBUYUKI
(Kowa Fujiken)
MORIWAKI TETSUO
(Kowa Fujiken)
YAMADA HIDEKI
(Kowa Fujiken)
KOGA TERUJI
(Kowa Fujiken)
TANAKA MASAHIRO
(Kowa Fujiken)
OGUMA YOSHIHIRO
(Biomedical Lab. Inc., JPN)
YOKOTA FUMIO
(Biomedical Lab. Inc., JPN)
NAKAJIMA MADOKA
(Biosafety Res. Cent., Foods, Drugs and Pestic.)
TAKIMOTO MASAYOSHI
(Kowa Fujiken)
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Journal Title;Pharmacometrics
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Journal Code:S0617A
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ISSN:0300-8533
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VOL.57;NO.1/2;PAGE.1-12(1999)
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| Figure&Table&Reference;FIG.2, TBL.5, REF.17 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;(+)-Monocalcium bis[(3R,5S,6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]-3,5-dihydroxy-6-heptenoate]* (NK-104), a novel HMG-CoA reductase inhibitor, was assessed for its mutagenicity using a bacterial reverse mutation test, a chromosomal aberration test in vitro and a mouse micronucleus test. The bacterial reverse mutation test was performed in four strains of Salmonella typhimurium (TA100, TA1535, TA98 and TA1537) and in a strain of Escherichia coli (WP2 uvrA) with metabolic activation (156 to 5,000.MU.g/plate) or without (10 to 313.MU.g/plate). The number of revertant colonies did not increase when compared with the vehicle control in any strain at any concentration. The chromosomal aberration was examined using cultured Chinese hamster lung cells. No significant increase of structural aberration was observed without metabolic activation up to the maximum dose of 6.2.MU.g/ml on each treatment (24 and 48hr). On the other hand, in the system with metabolic activation, an increase in the incidence of aberrant cells was observed at 625.MU.g/ml on 6hr treatment. In a confirmatory experiment, the induction of structural aberrations was reproduced at the range from 468.5 to 938.MU.g/ml. In any test, no statistically significant change was shown in the polyploidy. In the micronucleus test using bone marrow cells of male Crj: CD-1 mice treated with oral single administration at the doses of 250, 500 and 1,000mg/kg, the incidence of micronucleated polychromatic erythrocytes did not differ significantly from that in the concurrent controls. From these results, NK-104 has clastogenicity in vitro, but showed no bacterial mutation. Moreover, no mutagenic activities of NK-104 were shown in a mouse micronucleus test and a rat UDS test. It is suggested that clastogenic potential of NK-104 is not induced in vivo. (author abst.) |
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