In vitro Chromosomal Aberration Test on Amrubicin Hydrochloride(SM-5887) in Chinese Hamster Ovary Cells(CHO-K1).

Accession number;99A0241098
Title;In vitro Chromosomal Aberration Test on Amrubicin Hydrochloride(SM-5887) in Chinese Hamster Ovary Cells(CHO-K1).
Author; KOGISO SHIGEFUMI (Sumitomo Chemical Co., Ltd.) HARA MASAKI (Sumitomo Chemical Co., Ltd.) KATO HIROSHI (Sumitomo Chemical Co., Ltd.) ODAWARA KYOKO (Sumitomo Chemical Co., Ltd.) YOSHITAKE AKIRA (Sumitomo Chemical Co., Ltd.)
Journal Title;Japanese Pharmacology & Therapeutics
Journal Code:Z0947A
ISSN:0386-3603
VOL.27;NO.Suppl.1;PAGE.S.503-S.508(1999)
Figure&Table&Reference;TBL.2, REF.6
Pub. Country;Japan
Language;Japanese
Abstract;The clastogenic potential of amrubicin hydrochloride(SM-5887) was examined by an in vitro chromosomal aberration test using Chinese hamster ovary cells(CHO-K1) in the presence and absence of a rat liver drug-metabolizing enzyme system(S9 mix). In the direct method, the cells were treated with the test material for 24hr and 48hr in the absence of S9 mix. In the metabolic activation method, the cells were treated with the test material for 6hr in the presence of S9 mix followed by 18hr culture in fresh medium. The cytotoxicity test was conducted at concentrations ranging from 5*10-7 to 5*10-5M(test 1) or 1*10-8 to 5*10-7M(test 2) to determine the concentrations to be used in the chromosomal aberration test. In the chromosomal aberration test, dose levels ranging from 5*10-9 to 5*10-8M were selected in the direct method. In the metabolic activation method, concentrations ranging from 1*10-8 to 1*10-7M were used. The test material induced significant increases in the incidence of chromosomally aberrant cells in any treatment conditions. Positive control chemicals, mitomycin C(direct method), and benzo[a]pyrene(metabolic activation method) induced marked increases in the incidence of structurally aberrant cells. Based on these findings, it is concluded that SM-5887 has a potential to induce chromosomal aberrations against CHO-K1 cells under the conditions tested. (author abst.)