Extracellular genomic DNA protects mice against radiation and chemical mutagens

• Published in: GenomeBiology.com Vol. 5; no. 2; p. P3
• Main Authors: Yakubov, Leonid, Popova, Nelly, Nikolin, Valery, Semenov, Dmitry, Bogachev, Sergei, Oskina, Irina
• Format: Journal Article
• Language: English
• Published: BioMed Central Ltd 30.12.2003
• ISSN: 1465-6906; 1465-6914
• DOI: 10.1186/gb-2003-5-2-p3

BACKGROUND: High doses of ionizing irradiation and chemical mutagens induce random mutations and chromosome aberrations in cells of affected organisms and cause acute symptoms, delayed increased risk of cancer and accelerated aging. The mechanism of disease development remains unclear and no treatment exists for consequences of the mutagenic damage. HYPOTHESIS: We have proposed recently that extracellular genomic DNA from tissue fluids of a healthy organism, innate receptor-mediated nuclear delivery of this DNA, and its homologous recombination with cellular genomic sequences might function concertedly as a natural proofreading mechanism for somatic cell genomes. Here we hypothesize that cells dying from irradiation or chemical mutagens release heavily damaged DNA fragments that propagate mutations and chromosome aberrations to DNA-recipient cells via this mechanism, inducing cell death and release of their mutated DNA again into the bloodstream. The repeated release of the mutated DNA followed by its incorporation into cellular genomes would spread mutational damage in the affected organism, thus making this DNA the etiologic agent of either radiation sickness or post-mutagen exposure syndrome. The hypothesis opens a possibility to inhibit and treat the disease via administration of non-mutated genomic DNA fragments that would compete with the circulating mutant DNA fragments, entering cells in greater numbers, leading to replacement of mutant segments in cellular genomes. RESULTS AND CONCLUSIONS: Injection of fragmented mouse DNA, but not human DNA, into lethally irradiated mice dramatically increased their survival. Similarly, the mouse DNA was more potent than human and salmon DNA in accelerating recovery of the normal leukocyte level in mice treated with the chemical mutagen cyclophosphamide. The species specificity of the DNA therapy suggests that the genomic sequences are the agent producing the effects.