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[Cancer Research 35, 3146-3153, November 1, 1975]
© 1975 American Association for Cancer Research

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Recovery of a DNA-Protein Complex in Cultured Mammalian Cells from Damage Caused by 4-Nitroquinoline 1-oxide1

Toshinori Ide, Masaki Nakane and Toshiwo Andoh

Department of Virology, The Institute of Medical Science, The University of Tokyo, Shirokanedai 4-6-1, Minatoku, Tokyo, Japan

Treatment of FM3A cells with 4-nitroquinoline 1-oxide caused a decrease in the sedimentation velocity of a DNA-protein complex, but did not cause a dissociation of the complex, as revealed by neutral sucrose gradient centrifugation. Microscopic autoradiography of the complex spread on a Millipore filter, demonstrated that treatment of the cells with 4-nitroquinoline 1-oxide, or of the complex with Pronase E, gave rise to a relaxed mass of DNA fibers, in contrast to a compact mass of DNA from control cells.

The damage to the DNA-protein complex was repaired completely by incubation of the cells in a medium without 4-nitroquinoline 1-oxide. The following metabolic inhibitors had no effect on the repair of the complex: inhibitors of nucleic acid synthesis, {alpha}-amanitine, cordycepin, 2-mercapto-1-(β-4-pyridethyl)benzimidazol, 1-β-D-arabinofuranosylcytosine, 5-fluorodeoxyuridine, and hydroxyurea; inhibitors of protein synthesis, cycloheximide and puromycin; an inhibitor of the dark repair process in a variety of biological systems, caffeine; inhibitors of the microtubular and microfilament system, Colcemid and cytochalasin B, respectively; and inhibitors of energy metabolism, 2,4-dinitrophenol, KCN, iodoacetic acid, ouabain, and an atmosphere of nitrogen. Acriflavine and actinomycin D, which are known to intercalate into DNA, caused a decrease in the sedimentation velocity of the DNA-protein complex; therefore, the effects of these agents on the recovery process remained unsolved.

The repair process of the complex was, however, demonstrated to be temperature dependent. The process was inhibited at 10°, retarded at 28°, but accelerated at 40° as compared with the rate at 37°.

1 This study was supported in part by grants for cancer research from the Japanese Ministry of Education.

Received 12/30/74. Accepted 7/ 8/75.







HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
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Copyright © 1975 by the American Association for Cancer Research.