2. Academic Validation
  3. Enhancement of the Clastogenic Effects of Topotecan In Vivo by Tyrosyl-DNA Phosphodiesterase 1 Inhibitors

Enhancement of the Clastogenic Effects of Topotecan In Vivo by Tyrosyl-DNA Phosphodiesterase 1 Inhibitors

  • Bull Exp Biol Med. 2024 May;177(1):30-34. doi: 10.1007/s10517-024-06125-9.
A K Zhanataev 1,  A V Kulakova 2,  O A Luzina 3,  T M Khomenko 3,  K P Volcho 3,  N F Salakhutdinov 3,  A D Durnev 2
Affiliations

Affiliations

  • 1 V. V. Zakusov Research Institute of Pharmacology, Moscow, Russia. azhanataev@yandex.ru.
  • 2 V. V. Zakusov Research Institute of Pharmacology, Moscow, Russia.
  • 3 N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia.
PMID: 38954304 DOI: 10.1007/s10517-024-06125-9
Abstract

Topotecan administered intraperitoneally at single doses of 0.25, 0.5, and 1 mg/kg induced chromosomal aberrations in bone marrow cells of F1(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.

Keywords

bone marrow; chromosomal aberrations; mice; topotecan; tyrosyl-DNA phosphodiesterase inhibitors.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-161853
    99.69%, TDP1 Inhibitor