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Spontaneous Release of DNA by Human Blood Lymphocytes as Shown in an in Vitro System¹

Division of Onco-Hematology, Department of Medicine, Cantonal Hospital, 1205 Geneva [P. A., P. A. M.] and Department of Plant Physiology, Faculty of Science, University of Geneva, 1211 Geneva 4, Switzerland [M. S.]

Human blood lymphocytes released DNA in vitro in the absence of any stimulation. Once purified from the complex appearing in the supernatant, this DNA exhibited typical characteristics as shown by its UV absorption curve, its deoxyribose coloration, and its sensitivity to DNase. Elution patterns on hydroxyapatite columns indicated that the excreted DNA is double stranded. The released DNA was smaller than the cellular DNA; its molecular weight ranged from 3.5 x 10⁵ to 3.7 x 10⁶ daltons.

The DNA appearing in the supernatant does not seem to be due to dead or dying cells since: (a) the same amount of DNA was found in the medium whether the incubation lasted 2 hr or as long as 16 hr; (b) cell death rate had no effect on the amount of extracellular DNA; (c) when the lymphocytes were centrifuged and placed in a new medium several times in a row, a similar amount of extracellular DNA was isolated from each of the successive supernatants, whereas if, after centrifugation, the lymphocytes were put back in their original medium, no increase in the amount of extracellular DNA was observed, suggesting an active regulatory mechanism independent of a mechanical effect; (d) it took more than 1 hr for extracellular DNA to reach its maximum concentration, a fact that also argues against a mechanical effect; (e) the specific activity of the released DNA was different from that of the cellular DNA, depending on the time of labeling; and (f) the cells that had excreted DNA kept their functional integrity, as shown by their fully maintained capacity to increase DNA synthesis after stimulation.

The extracellular DNA hybridized specifically with cellular DNA. The hybridization curves indicate that the DNA excreted is highly complex, and they suggest that it is composed of part of the newly synthesized DNA. The higher specific activity of the released DNA, compared with that of the cellular DNA after a long labeling period, can be explained only by a preferential release of the newly synthesized DNA.

¹ This work was supported by grants from the Ligue Genevoise contre le Cancer, from the Ligue Suisse contre le Cancer, from the Fonds National Suisse de la Recherche Scientifique Nos. 3776.72 and 3832.72, from the Seidl Hentsch Fund, and from the O.J. Isvet Fund Nos. 101 and 102.

Received 3/ 7/74. Accepted 5/19/75.

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