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• W2007646022 abstract "A single dose of 9-hydroxy-ellipticine, 2-N-methyl-9-hydroxy-ellipticine, 9-fluoro-ellipticine, and 9-amino-ellipticine (5 to 10 mg/kg body wt, ip) resulted in murine bone marrow toxicity as shown by chromosome clumping, chromatid aberrations, and micronuclei formation. An increase in sister chromatid exchanges (SCE) was also observed. These effects are most likely directly related to the topoisomerase inhibitory effect of these drugs since topoisomerase II is involved in the separation of intertwined chromosomal DNA molecules during mitosis as well as being a mediator of DNA exchanges. The two antitumor drugs 2-N-methyl-9-hydroxy-ellipticine and 9-hydroxy-ellipticine were most genotoxic with chromosome abnormalities occurring in 33-95% of the cells and SCE on the order of 12.3 to 19.2 events per cell. Both of these drugs show high topoisomerase II inhibitory activity in vitro. In contrast, 9-amino-ellipticine and 9-fluoro-ellipticine were less genotoxic with chromosomal abnormalities occurring in 14-17% of the cells and SCE on the order of 7.1 to 7.7 events per cell. These two derivatives are both inactive toward experimental tumors and show less topoisomerase II inhibitory activity in vitro. Our results suggest that the ellipticine drugs owe at least some of their cytotoxicity to their genotoxic effects, which seem to be mediated through interaction with topoisomerase II." @default.
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• W2007646022 date "1987-06-01" @default.
• W2007646022 modified "2023-09-25" @default.
• W2007646022 title "In vivo exposure to four ellipticine derivatives with topoisomerase inhibitory activity results in chromosome clumping and sister chromatid exchange in murine bone marrow cells" @default.
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• W2007646022 doi "https://doi.org/10.1016/0041-008x(87)90049-4" @default.
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