Institute of Toxicology of Federal Medico-Biological Agency
The objects of this study were lymphocytes and reticulocytes of white rat blood.
The aim of this work is to compare the mutagenic and cytotoxic effects of N-nitrosodimethylamine (NDMA) using two kinds of the micronucleus test: on reticulocytes and on lymphocytes using the cytokinesis-block micronucleus (CBMN) assay.
The mutagenicity and cytotoxicity were explored after the acute intraperitoneal administration of NDMA in doses of 7.5, 15 and 30 mg/kg at 3 and 24 hours exposure and after daily administration of NDMA in doses of 3.5 and 7 mg/kg for 7 and 14 days.
In studies where a micronucleus test on reticulocytes after acute and subchronic administration of NDMA was used, mutagenicity was not detected. The cytotoxic effect on reticulocytes was shown after administering NDMA daily for 7 and 14 days. The decline of the relative content of reticulocytes after the subchronic administration suggests the masking of the mutagenic effect of NDMA by its cytotoxicity.
In case of CBMN assay, the mutagenicity of NDMA was detected in 24 hours after administration in doses of 15 and 30 mg/kg, and the cytotoxic effect was detected after an injection of 30 mg/kg.
In experiments after subchronic administration of NDMA, mutagenic and cytotoxic effects were revealed after daily injections for 7 days at a dose of 7 mg/kg, and after 14 days the mutagenicity acquired a dose-dependent character after administration in doses of 3.5 and 7 mg/kg. The cytotoxic effect was shown only at a dose of 7 mg/kg.
Thus, the obtained results proved the possibility of using lymphocytes in the monitoring studies of the mutagenic action of NDMA. Also proven were the high sensitivity and reliability of the CBMN assay method and its independence from the cytotoxic effect of testing the mutagenicity of NDMA using the micronucleus test on lymphocytes in a cytokinesis-block culture.
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