[The presence of mtDNA-like sequences in the DNA of liver chromatin fractions from rats of different ages].

We have used young (2-3 months), adult (6-8 months) and old (26-28 months) rats. Nuclear DNA (nDNA) was isolated from the liver nuclei and chromatin fractions (RCh, repressed chromatin; ACh, transcriptionally active chromatin; MCh, membrane-bound chromatin) and thereafter loaded on nitrocellulose filters. Hybridization was carried out with radioactively labelled mitochondrial DNA (mtDNA) as a probe mtDNA was first isolated from the liver mitochondria of adult rats and then labelled in nick-translation reaction with 32P-dCTP. Radioautography densitometry data have shown that the content of mtDNA-homologous sequences in the liver nDNA was decreased in adult rats (56%) and increased in the old ones (240%), as compared with the young animals. mtDNA-homologous sequences were localized in the young rats mainly in the RCh, while the adult and old rats had similar sequences in the ACh. We suggest that the age-related dynamics of mtDNA-homologous sequences was due to various factors. At the early stages cell differentiation proceeds rapidly and is accompanied by structural and functional reorganization of both nuclear and mitochondrial genomes. These changes increase the probability of contacts and integration of mtDNA fragments and whole molecules in the nuclear genome. As a result, an elevated level of mtDNA-homologous sequences is observed in the liver nuclear genome of young rats. In adult rats, repair and elimination of cells with defective nDNA and decreased proliferation of hepatocytes account for decreased amounts of mtDNA-homologous sequences in nDNA. In old animals, the repair to destruction ratio shifts towards destruction and, hence, mtDNA-homologous sequences are accumulated in the liver nDNA. Age related dynamics of mtDNA-homologous sequences in the liver chromatin fractions is characterized by accumulation of these sequences in ACh and MCh chromatin fractions during maturation and ageing. This also confirms our suggestion that integration of mtDNA-homologous sequences in the nuclear genome is due to various mechanisms operational at the early and late stages of ontogenesis.