%0 Journal Article
%T Enhancement of the Clastogenic Effects of Topotecan In Vivo by Tyrosyl-DNA Phosphodiesterase 1 Inhibitors.
%A Zhanataev AK
%A Kulakova AV
%A Luzina OA
%A Khomenko TM
%A Volcho KP
%A Salakhutdinov NF
%A Durnev AD
%J Bull Exp Biol Med
%V 0
%N 0
%D 2024 Jul 2
%M 38954304
%F 0.737
%R 10.1007/s10517-024-06125-9
%X 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.