酪氨酸-DNA 磷酸二酯酶 1 抑制剂增强拓扑替康的体内致裂效应。
Enhancement of the Clastogenic Effects of Topotecan In Vivo by Tyrosyl-DNA Phosphodiesterase 1 Inhibitors.
机构信息
V. V. Zakusov Research Institute of Pharmacology, Moscow, Russia.
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia.
出版信息
Bull Exp Biol Med. 2024 May;177(1):30-34. doi: 10.1007/s10517-024-06125-9. Epub 2024 Jul 2.
Topotecan administered intraperitoneally at single doses of 0.25, 0.5, and 1 mg/kg induced chromosomal aberrations in bone marrow cells of F(CBA×C57BL/6) hybrid mice in a dose-dependent manner. A tyrosyl-DNA phosphodiesterase 1 (TDP1) inhibitor, an usnic acid derivative OL9-116 was inactive in a dose range of 20-240 mg/kg, but enhanced the cytogenetic effect of topotecan (0.25 mg/kg) at a dose of 40 mg/kg (per os). The TDP1 inhibitor, a coumarin derivative TX-2552 (at doses of 20, 40, 80, and 160 mg/kg per os), increased the level of aberrant metaphases induced by topotecan (0.25 mg/kg) by 2.1-2.6 times, but was inactive at a dose of 10 mg/kg. The results indicate that TDP1 inhibitors enhance the clastogenic activity of topotecan in mouse bone marrow cells in vivo and are characterized by different dose profiles of the co-mutagenic effects.
拓扑替康以 0.25、0.5 和 1 mg/kg 的腹腔内单剂量给药，以剂量依赖的方式诱导 F(CBA×C57BL/6)杂交小鼠骨髓细胞中的染色体畸变。一种酪氨酰-DNA 磷酸二酯酶 1（TDP1）抑制剂，一种乌苏酸衍生物 OL9-116，在 20-240 mg/kg 的剂量范围内没有活性，但在 40 mg/kg（口服）的剂量下增强了拓扑替康（0.25 mg/kg）的细胞遗传学效应。TDP1 抑制剂，一种香豆素衍生物 TX-2552（口服 20、40、80 和 160 mg/kg），将拓扑替康（0.25 mg/kg）诱导的异常中期的水平提高了 2.1-2.6 倍，但在 10 mg/kg 的剂量下没有活性。结果表明，TDP1 抑制剂增强了拓扑替康在体内小鼠骨髓细胞中的致裂活性，并且具有不同的协同诱变作用剂量曲线。
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