ABSTRACT
Male BALB/c mice with streptozotocin-induced diabetes mellitus were used to study nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) damage using comet DNA assay and real-time PCR, respectively. In animals receiving single injection of streptozotocin in a dose of 200 mg/kg, severe hyperglycemia was observed on days 10 and 21 of the experiment, while after 5-fold administration of streptozotocin in a dose of 40 mg/kg, it developed on days 14 and 28. DNA damage and the level of atypical DNA comets in the liver increased both on days 10 and 21 after single administration of streptozotocin, and on days 14 and 28 after repeated administrations. The level of atypical DNA comets on day 21 after a single administration of streptozotocin increased in the kidneys, but not in the brain, testes, and pancreas. Real-time PCR revealed mtDNA damage in the liver, kidney, and pancreatic cells of mice with streptozotocin-induced diabetes. Thus, these animal models were found to reproduce pathognomic signs of diabetes, hyperglycemia, and nDNA damage; mtDNA damage was also detected.
Subject(s)
Diabetes Mellitus, Experimental , Hyperglycemia , Mice , Male , Animals , DNA, Mitochondrial/genetics , Streptozocin , Mice, Inbred BALB C , Hyperglycemia/chemically induced , Hyperglycemia/genetics , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/genetics , DNA DamageABSTRACT
Aneugenic effects of the chemicals with antitumor activity were studied in mouse oocytes in vivo by cytogenetic analysis. In control mice, no oocytes with numerical chromosome aberrations were found. Colchicine (0.2-4 mg/kg), paclitaxel (2.5-7.5 mg/kg), and etoposide (10-60 mg/kg) produced a significant dose-dependent aneugenic effects (induction of up to 25% aneuploid oocytes) and increased the yield of oocytes arrested in the meiotic MI stage and with premature separation of sister chromatid. Paclitaxel induced up to 20% polyploid chromosomes. Doxorubicin (2.5 mg/kg), melphalan (10 mg/kg), and cisplatin (5-10 mg/kg) exhibited weak aneugenic activity (induction of up to 5% aneuploid oocytes). Cyclophosphamide (10-80 mg/kg) had minor effect on the studied parameters. Methotrexate (25-200 mg/kg) exhibited no aneugenic activity, but significantly increased the level of polyploid cells. The observed aneugenic effects included hypo- and hyperploidy in various proportions or hypoploidy, but no solely hyperhaploidy.
Subject(s)
Doxorubicin/pharmacology , Aneugens , Aneuploidy , Animals , Cisplatin/pharmacology , Colchicine/pharmacology , Etoposide/pharmacology , Melphalan/pharmacology , Mice , Oocytes/drug effects , Oocytes/metabolism , Paclitaxel/pharmacology , PolyploidyABSTRACT
The influence of N-acetylcysteine (ACC) on the cytogenetic effects of etoposide in F1 CBA x C57BL/6 mice was studied. Etoposide introduced intraperitoneally in doses of 10, 20, 40, and 60 mg/kg has a dose-dependent clastogenic activity and has an aneugenic effect with the induction of mainly hypohaploid oocytes. ACC significantly decreases the aneugenic and clastogenic activity of etoposide (20 mg/kg) in oocytes of 6-, 9-, and 12-week-old mice during triple introduction at a dose 200 mg/kg per os. The most pronounced anticlastogenic ACC activity (an 80% decrease) was registered in 9-week-old females; a 100% decrease in aneugenesis was detected in 6-week-old female mice.
Subject(s)
Acetylcysteine/administration & dosage , Chromosome Aberrations/drug effects , Mutagenesis/drug effects , Oocytes/drug effects , Animals , Etoposide/toxicity , Female , Mice , Mutagens/toxicity , Oocytes/growth & developmentABSTRACT
We developed an original method of isolation and analysis of cytogenetic micropreparations of mouse oocytes including treatment with buffered hypotonic saline, paraformaldehyde fixation, and fluorescent staining. The method had several advantages, including high quality of sections and low labour intensity.
Subject(s)
Cytogenetic Analysis , Oocytes/physiology , Animals , Cells, Cultured , Chromosomes, Mammalian/metabolism , Female , Meiosis , Metaphase , Mice , Mice, Inbred C57BL , Mice, Inbred CBA , SuperovulationABSTRACT
We studied DNA-damaging effects of dental bleaching systems containing hydrogen peroxide and/or carbamide peroxide by the "comet assay" (alkaline version). Dental bleaching systems in a hydrogen peroxide concentration range from 0.03 to 30 mM produced a genotoxic effect on isolated HeLa cells in vitro comparable with the effects of pharmacopoeial hydrogen peroxide or urea peroxide. Catalase protected the cells against products containing hydrogen peroxide and had no effect on the genotoxicity of samples containing carbamide peroxide.
