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Injections ofexogenous DNAin combination witha cytostatic agent cyclophosphamide (CP) cause illness anddeathofexperimental mice. This phenomenon is referredto this as delayeddeath. It has been foundthat upon intraperitoneal injections fragments ofexogenous DNAreachthe bone marrowniche andenter the nuclei ofbone marrowcells (BMCs). Also, fragments ofexogenous DNAare capturedfrom culture medium byBMCs generatedex vivo. Upon suchtreatment, the fragments are incorporatedinto cells in a non-degradedform. We estimate that under suchconditions upto 1800 kb ofexogenous DNAcan be present in BMCs as fragments. After ex vivo incubation withBMCs, fragments ofexogenous DNAinternalizedin cells ofbothintact andCP pre-treatedmice become circularized. It has been shown that fragments ofexogenous DNAcan form high-molecular weight structures in vivo. Moreover, fragments localizedin BMCnuclei are suggestedto integrate into chromosome(s) ofrecipient mouse genomes when treatedwithCP andexogenous DNA.

Injections of exogenous DNA combined with a cytostatic agent cyclophosphamide (CP) cause illness and death in experimental mice. This phenomenon is referred to as delayed death. It has been found that fragments of exogenous DNA reach the bone marrow and enter the bone marrow cells (BMCs) 1-5 min after injections. Fragments of exogenous DNA are captured from culture medium by BMCs generated ex vivo. After joint incubation with BMCs of mice, the fragments of exogenous DNA are internalized into internal compartments in a nondegraded form. Up to 1800 kb of nucleic acid material can be present in each cell of BMCs generated ex vivo and treated with fragments of exogenous DNA. The fragments of exogenous DNA internalized in BMCs generated ex vivo of both intact and CP pretreated mice become circularized. In the case of intact mice, the fragments of exogenous DNA can form high-molecular weight structures in vivo. It is suggested that the exogenous fragments localized in BMC nuclei integrate into chromosome(s) of the recipient mouse genome when treated with CP and exogenous DNA. [ABSTRACT FROM AUTHOR]