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Derepression of Nuclear Template Restrictions for DNA Synthesis by the Immunostimulator Pyran Copolymer

Viral Biology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20014

Pyran copolymer (NSC 46015) is a polyanionic compound of varying molecular weight and is a well-known interferon inducer. Recently, pyran has received considerable attention because of its strong macrophage-activating and immunopotentiating properties and their application in various oncological systems. The mechanism(s) of action for these various biological phenomena remains unknown. We herein report that pyran is capable of interacting with the repressed genome of isolated murine liver nuclei in such a way as to allow DNA synthesis to take place, when assayed with exogenous bacterial DNA polymerase. This interaction occurred immediately and was influenced by the magnesium concentration, pyran concentration, and molecular weight of the pyran. Furthermore, pyran could reverse the histone-induced inhibition of a pure poly(deoxyadenylate-deoxythymidylate) template primer for DNA synthesis. None of these observations was due to interaction of pyran with the nuclear membrane, because parallel results were obtained whether intact nuclei or nuclei that had undergone membrane disruption were used. In addition, morphological swelling of the nuclei was seen when in the presence of pyran concentrations that were maximally stimulatory to DNA synthesis. Pyran, therefore, is able to release the DNA template of murine liver nuclei from restrictions that normally would prevent them from serving as a useful template for DNA synthesis. It remains unclear whether these observations are directly relevant to the mechanisms of action that explain the broad biological activity of pyran, but the phenomenon is one that should not be overlooked.

¹ Present address: Division of Urology, University of Colorado Medical Center, Denver, Colo. 80220.

² To whom requests for reprints should be addressed.

Received 9/26/77. Accepted 3/ 8/78.