Title: In vivo study of genotoxicity and teratogenicity of silica nanocrystals

Authors: Andrey D. Durnev, Anna S. Solomina, Ekaterina D. Shreder, Elena P. Nemova, Olga V. Shreder, Natalya O. Daugel'-Dauge, Aliy K. Zhanataev, Vasilissa A. Veligura, Lyubov A. Osminkina, Maxim B. Gongalsky, Victor Yu. Timoshenko, Sergey S. Seredenin

Addresses: Science Research Institute of Pharmacology, Russian Academy of Medical Sciences, Baltiyskaya str.8, Moscow, 125315, Russia. ' Division of Drug Toxicology, Science Research Institute of Pharmacology, Russian Academy of Medical Sciences, Baltiyskaya str.8, Moscow, 125315, Russia. ' Division of Drug Toxicology, Science Research Institute of Pharmacology, Russian Academy of Medical Sciences, Baltiyskaya str.8, Moscow, 125315, Russia. ' Division of Drug Toxicology, Science Research Institute of Pharmacology, Russian Academy of Medical Sciences, Baltiyskaya str.8, Moscow, 125315, Russia. ' Division of Drug Toxicology, Science Research Institute of Pharmacology, Russian Academy of Medical Sciences, Baltiyskaya str.8, Moscow, 125315, Russia. ' Laboratory of Pharmacology of Mutagenesis, Science Research Institute of Pharmacology, Russian Academy of Medical Sciences, Baltiyskaya str.8, Moscow, 125315, Russia. ' Laboratory of Pharmacology of Mutagenesis, Science Research Institute of Pharmacology, Russian Academy of Medical Sciences, Baltiyskaya str.8, Moscow, 125315, Russia. ' Physics Department, M.V. Lomonosov Moscow State University, Leninskiye Gory 1, 119991, Moscow, Russia. ' Physics Department, M.V. Lomonosov Moscow State University, Leninskiye Gory 1, 119991, Moscow, Russia. ' Physics Department, M.V. Lomonosov Moscow State University, Leninskiye Gory 1, 119991, Moscow, Russia. ' Physics Department, M.V. Lomonosov Moscow State University, Leninskiye Gory 1, 119991, Moscow, Russia. ' Science Research Institute of Pharmacology, Russian Academy of Medical Sciences, Baltiyskaya str.8, Moscow, 125315, Russia

Abstract: The potential genotoxicity of silica nanocrystals (nc-Si) (size 2-7 nm with their agglomerates 5 μm) in mice and influence of nc-Si on the embryonal and the postnatal development of the rats were evaluated. No clastogenic effects were observed in bone marrow cells of mice intraperitoneally exposed to single doses of nc-Si 5, 25 and 50 mg/kg for 24 hr or to doses 5 and 25 mg/kg for seven and 14 days. Comet assay revealed a significant increase in tail DNA percentage in the bone marrow cells of mice treated with nc-Si at a single dose 5 mg/kg for 24 h and both in bone marrow and brain cells when nc-Si was used at a dose 50 mg/kg. There was no significant increase in DNA damage after a 3 h treatment with nc-Si at doses 5 and 25 mg/kg. Also, no elevated DNA damage was observed in mice exposed to nc-Si at 5 mg/kg dose for seven days. Dose of nc-Si at 50 mg/kg caused death of 40-60% of the animals within 2-3 days that made impossible evaluation genotoxicity in this dose at long-term exposure. Nc-Si injected intraperitoneally to rats at a dose of 50 mg/kg on the 1st, 7th and 14th days of pregnancy showed no teratogenicity and had no influence on postnatal development of pups. But negative influence on body weight gain in pregnant rats and newborns at some stages of the experiment was noticed.

Keywords: silica nanocrystals; genotoxicity; teratogenicity; postnatal development; nanotechnology; embryo development; bone marrow cells; brain cells; mice; rats; pregnancy; newborns; silicon nanocrystals.

DOI: 10.1504/IJBNN.2010.034126

International Journal of Biomedical Nanoscience and Nanotechnology, 2010 Vol.1 No.1, pp.70 - 86

Published online: 15 Jul 2010 *

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