THE EXPERIMENTAL STUDY OF THE MUTAGENIC ACTION OF N-NITROSODIMETHYLAMINE IN MICE

Abstract

The mutagenic activity of N-nitrosodimethylamine (NDMA) in the laboratory mice was studied usingthe chromosome aberration test. It was established that NDMA with intraperitoneal single administration(acute experience) in doses of 2.0; 4,0 and 8,0 mg/kg induced chromosomal aberrations in the mouse bonemarrow cells with a frequency statistically significantly exceeding the control level. With an increase in thedose of xenobiotics, the frequency of aberrant cells increased by 2.23 (p <0.05); 3.00 (p <0.05) and 3.89(p <0.001) times, respectively. The dose dependence of the level of induced mutagenesis was revealed(r = 0.97, p = 0.03). A statistically significant increase in the level of aneuploid and polyploid cells wasestablished, however, no dose dependence was found (r = 0.85, p = 0.29). Prolonged intoxication ofNDMA (subacute experience, intoxication within 10 days) of experimental animals resulted in a statistically significant increase in the frequency of aberrant bone marrow cells and the number of chromosomalaberrations per 100 metaphase compared to intact animals and animals of acute experience. The dose ofNDMA 8 mg/kg, equal to 1/5 LD50, with repeated administration was lethal for all individuals. With repeated administration of NDMA at doses of 2.0 and 4.0 mg/kg, the frequency of aberrant cells increasedstatistically significantly in comparison with a single injection of 1.70 (p <0.001) and 1.60 (p <0.01), respectively, and the number of chromosomal aberrations per 100 metaphase is 1.73 (p <0.001) and 1.51 (p<0.01) times. With prolonged exposure to xenobiotic, the frequency of cells with genomic mutations alsoincreased statistically. The increase in the overall frequency of chromosomal aberrations occurred mainlydue to chromatin-type disorders. The mutagenic effect of N-nitrosodimethylamine on mice, established inour studies, may be due to an increase in the level of active forms of oxygen and the accumulation of lipidperoxidation products in the tissues of the body. Possible mechanisms of mutagenic and genotoxic actionof NDMA can be the enhancement of free radical processes and DNA methylation.Key words: N-nitrosodimethylamine, mutagenic effect, acute and subacute effects, chromosomalaberrations, genomic mutations.