The assessment of the level of genetic damages accumulated with age and induced in liver cells by the micronucleus production]

Latent genetic disturbances in aging liver cells can be registered during interphase by the appearance of micronuclei resulting from certain chromosomal aberrations. Micronuclei were also detected in postmitotic hepatocytes of mouse liver regenerating after partial resection of CCl4 poisoning. In 1.5- and 2-month-old mice, the proportion of micronuclei-containing cells was on average 0.59 and 0.89%, respectively. At the age of 4 and 7 months, the proportion of aberrant cells in hepatocyte population, including cells containing multiple micronuclei, increased to 5.93 and 11.7%, respectively. In order to evaluate parameters used to characterize "spontaneous" aging, experiments were performed in which genetic disturbances were induced by x-irradiation or treatment with dipin, an alkylating agent (individually or in combination); the effect was determined one and two months after the treatment. The yield of micronuclei under the conditions of a mild treatment (irradiation at a dose of 0.7 and 1.4 Gr or dipin at a dose of 30 mg/kg body weight) was similar to that observed during aging. The possible reasons for the increased (as compared to the published data) rate of genetic disturbances in arbitrary intact animals are discussed.