Detection of single-strand breaks in DNA induced by mitoxantrone in experimental tumors after in vivo treatment.
The fluorometric assay of DNA alkaline unwinding [15] was applied to murine tumor DNA after in vivo treatment. Mitoxantrone (MX) whose cytostatic effect has been extensively investigated was tested as DNA damaging compound. The single-strand breaks of DNA (SSB) in ascitic tumors (EAT. P388) and in solid tumors (B16a, B16) were detected after intraperitoneal administrations of 1 and 10 mg/kg MX in the course of 1 to 96 hours. The maximal number of SSB was measured after 1 to 6 hours and DNA damage outlasted 24 to 96 hours in dependence on the dose of MX and on the type of tumor. A dependence of DNA damage induced by MX on the route of tumor implantation was found. Ascitic tumor P388 and EAT were more than 5 times more sensitive to the effects of MX than solid melanomas. The SSB correlated well with the intracellular concentration of MX in the EAT cells.
Hubálek
F
F
Department of Drug Carcinogenesis, Czechoslovak Academy of Sciences.
D000818:Animals; D004249:DNA Damage; D004277:DNA, Single-Stranded / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D051379:Mice; D008942:Mitoxantrone / Q000008:administration & dosage / Q000627:therapeutic use*; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000235:genetics; D013997:Time Factors
D004277:DNA, Single-Stranded; D008942:Mitoxantrone