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Initial Degradation of Deoxyribonucleic Acid after Injection in Mammals¹

( Laboratoire de Biochimie et Enzymologie et Laboratoire d'Ultracentrifugation, Institut Gustave Roussy, Villejuif (Seine), France)

The fate of DNA² in the blood of rabbits and mice, after i.v. and i.p. injection, has been followed by viscosimetry and chemical determination of acid-precipitable DNA. It has been shown that the initial degradation of DNA is due to neutral DNase activity, which sets up a very effective biochemical barrier against exogenous DNA. The change in molecular weight of DNA administered in vivo has been calculated and correlated with the time after which physical properties of DNA are not consistent with biologic activity. This time can be expected to vary from a few sec to about 10 min in animal species with low plasma DNase level, such as man. It can be increased by using DNase-inhibitors like methyl green.

Although it is unlikely that a large amount of highly polymerized DNA could reach cells without previous depolymerization after i.v. administration, our results are compatible with the expression of any infecting or transforming properties of this material.

¹ This work has been done under Contract 61-FR-060 with the Comité Cancer et Leucémie de la Délégation Générale à la Recherche Scientifique et Technique.

² The following abbreviations are used: DNA, native deoxyribonucleic acid as extracted by usual methods; insol-DNA, polydesoxyribonucleotides insoluble in perchloric acid (PCA) under usual conditions; sol-DNA, oligonucleotides soluble in PCA (we did not find a report or publication of the M.W. of polydeoxyribonucleotides and acid precipitability, but, one can suppose that the M.W. is low since an exhaustive enzymatic attack of DNA is necessary before the appearance of sol-DNA is observed; DNase, neutral deoxyribonuclease(s) of blood plasma; MG, methyl green; KU, Kurnick unit (10) for neutral DNase activity; [], intrinsic viscosity expressed in c.g.s. units; P, molar coefficient of extinction (260mµ) calculated from phosphorus concentration.

Received 10/ 2/64. Revised 2/ 3/65.