Blagoeva P M, Balansky R M, Mircheva T J, Simeonova M I
Laboratory of Chemical Mutagenesis and Carcinogenesis, National Centre of Oncology, Sofia, Bulgaria.
Mutat Res. 1992 Jul;268(1):77-82. doi: 10.1016/0027-5107(92)90085-g.
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.
采用沙门氏菌/微粒体诱变性试验以及小鼠骨髓和小鼠胎肝中的微核试验，研究了丝裂霉素C（MMC）和表柔比星（FR）以游离形式以及包载于聚氰基丙烯酸丁酯纳米粒（PBCN）中的遗传毒性作用。所获得的数据清楚地表明，MMC（0.25 - 2.00微克/平板）在鼠伤寒沙门氏菌TA102中是一种强诱变剂，而该化合物在PBCN中的相同浓度对诱导细菌细胞中的his+回复突变无效。当FR（1.0 - 20.0微克/平板）包载于PBCN中时，在鼠伤寒沙门氏菌TA98中也观察到其诱变活性完全被抑制。此外，将MMC（2.0或4.0毫克/千克，腹腔注射）包载于PBCN中，分别显著降低或甚至消除了其在未孕和怀孕小鼠骨髓以及小鼠胎肝中的致断裂活性。另外，还证实仅PBCN缺乏遗传毒性作用。MMC包载于PBCN后，其在小鼠骨髓中的毒性活性显著降低或完全消除。可以得出结论，一些抗肿瘤药物包载于PBCN后，其遗传毒性活性可能会显著降低甚至消除。
