Reverse Mutation Test of Amrubicin Hydrochloride(SM-5887) in Bacterial Systems.
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Accession number;99A0241097
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| Title;Reverse Mutation Test of Amrubicin Hydrochloride(SM-5887) in Bacterial Systems. |
| Author;
KOGISO SHIGEFUMI
(Sumitomo Chemical Co., Ltd.)
YAMADA FUMIHIRO
(Sumitomo Chemical Co., Ltd.)
KITAMOTO SACHIKO
(Sumitomo Chemical Co., Ltd.)
YOSHITAKE AKIRA
(Sumitomo Chemical Co., Ltd.)
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Journal Title;Japanese Pharmacology & Therapeutics
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Journal Code:Z0947A
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ISSN:0386-3603
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VOL.27;NO.Suppl.1;PAGE.S.497-S.502(1999)
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| Figure&Table&Reference;TBL.3, REF.7 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;Amrubicin hydrochloride(SM-5887) was evaluated for its mutagenic potential by the reverse mutation test with four strains of Salmonella typhimurium(TA100, TA98, TA1535 and TA1537) and one strain of Escherichia coli(WP2uvrA). The test was conducted by the preincubation method with and without a drug-metabolizing enzyme system(S9 mix). Since SM-5887 showed cytotoxicity at higher doses in the dose-finding assay, the main assays were conducted at dose levels ranging from 100 to 5000.MU.g/plate for all strains in the absence of S9 mix, from 10 to 500.MU.g/plate for four strains of Salmonella typhimurium in the presence of S9 mix, and from 100 to 5000.MU.g/plate for the strain of Escherichia coli in the presence of S9 mix. The main assays were conducted twice. Precipitates of the test chemical were observed at 500.MU.g/plate and above concentrations both in the presence and the absence of S9 mix. SM-5887 did not increase the number of revertant colonies at least twice as many as those of the solvent control in TA100, TA98, TA1535 or WP2uvrA. As for TA1537, SM-5887 showed a slight increase in the number of revertant colonies without S9 mix and a marked dose-dependent increase(42-66 times as many as those of the solvent control) with S9 mix. The positive control chemicals, methylmethanesulfonate, 2-nitrofluorene, sodium azide, ICR-191, N-ethyl-N'-nitro-N-nitrosoguanidine, benzo(a)pyrene and 2-aminoanthracene showed marked increases in the number of revertant colonies. Based on these results, it is concluded that SM-5887 is mutagenic under the test conditions. (author abst.) |
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