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Translocation of DNA from the Vascular into the Nuclear Compartment of Solid Mammary Tumors

Laboratory of Biochemistry, National Cancer Institute, NIH, Bethesda, Maryland 20014

Fragments of DNA-³H, with molecular weights of several million, could be concentrated in vivo in the nuclei of Walker carcinomas. DNA-³H was obtained from lactating mammary glands of the same strain of rats bearing the tumor or from Micrococcus lysodeikticus. The degradation of DNA-³H by blood was small if the infused fragments were large. The uptake by the tumor was about 10-fold better when DNA was given through the aorta than when given through the i.v. route. Total uptake by tumors infused for several days was 0.5 to 1.0% of total tumor DNA. The vascular walls maintained a gradient in concentration between blood and interstitial fluid of the tumor. This fluid was unable to degrade DNA-³H rapidly but usually contained only small DNA-³H fragments. The largest fragments were more extensively taken up by the cells. When the size of the DNA-³H fragments infused was the largest, the amount of high-molecular-weight DNA-³H isolated from the tumor nuclei was the highest. The nuclei always contained the largest amount of the incorporated DNA-³H. During the first half hr after the end of M. lysodeikticus DNA infusion, some of the injected DNA could be recovered from the nuclear pellet, which suggested that it probably reached the nuclei relatively intact.

¹ Visiting Scientist, Department de Radiobiologie, Centre d'Etude de l'Energie Nucleaire, Mol, Belgium.

² Address reprint requests to this author.

Received 2/16/71. Accepted 4/23/71.