Diminished genotoxicity of mitomycin C and farmorubicin included in polybutylcyanoacrylate nanoparticles.
The genotoxic effects of mitomycin C (MMC) and farmorubicin (FR) in a free form and included in polybutylcyanoacrylate nanoparticles (PBCN) were studied employing the Salmonella/microsome mutagenicity assay and the micronucleus test in mouse bone marrow as well as in mouse fetal liver. The data obtained clearly indicated that MMC (0.25-2.00 micrograms/plate) was a strong mutagen in S. typhimurium TA102, while the same concentrations of this compound in PBCN were ineffective in inducing his+ revertant mutations in bacterial cells. A similar total suppression of mutagenic activity of FR (1.0-20.0 micrograms/plate) was registered in S. typhimurium TA98 when the drug was included in PBCN. Furthermore, the incorporation of MMC (2.0 or 4.0 mg/kg, i.p.) into PBCN strongly diminished or even abolished its clastogenic activity in the bone marrow of virgin and pregnant mice as well as in mouse fetal liver, respectively. In addition, a lack of genotoxic effect of PBCN only was also established. The toxic activity of MMC in mouse bone marrow was significantly reduced or completely abolished after its inclusion in PBCN. A conclusion might be drawn that the genotoxic activity of some antitumor drugs might be markedly diminished or even abolished after their incorporation in PBCN.
Blagoeva
P M
PM
Laboratory of Chemical Mutagenesis and Carcinogenesis, National Centre of Oncology, Sofia, Bulgaria.
Balansky
R M
RM
Mircheva
T J
TJ
Simeonova
M I
MI
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D004337:Drug Carriers; D004659:Enbucrilate; D015251:Epirubicin / Q000633:toxicity*; D005260:Female; D008099:Liver / Q000187:drug effects / Q000196:embryology; D008431:Maternal-Fetal Exchange; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects; D015162:Micronucleus Tests; D016685:Mitomycin / Q000633:toxicity*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D011247:Pregnancy; D012486:Salmonella typhimurium / Q000187:drug effects
D004337:Drug Carriers; D009153:Mutagens; D015251:Epirubicin; D016685:Mitomycin; D004659:Enbucrilate