This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Painter, R. B. Search for Related Content PubMed PubMed Citation Articles by Painter, R. B.

Inhibition of DNA Replicon Initiation by 4-Nitroquinoline 1-Oxide, Adriamycin, and Ethyleneimine¹

Laboratory of Radiobiology, University of California, San Francisco, California 94143

The effects ot three widely differing chemical carcinogens, 4-nitroquinoline 1-oxide, Adriamycin, and ethyleneimine, on DNA replication were studied by pulse labeling of DNA with [³H]thymidine and sedimentation analysis with alkaline sucrose gradients. At doses that reduced the rate of DNA synthesis to 30 to 60% of control values, only ethyleneimine produced damage that resulted in lower molecular weights of parental DNA. All three chemicals inhibited replicon initiation, but to differing extents. Inhibition of replicon initiation was the first clearly identified effect of 4-nitroquinoline 1-oxide and was the main cause of inhibition of DNA synthesis. Ethyleneimine caused severe inhibition of replicon initiation, but blocks to chain elongation also contributed significantly to the inhibition of overall DNA synthesis. Adriamycin affected replicon initiation to a small but significant extent; the primary cause of inhibition of DNA synthesis by this drug was a slowing of the rate of chain elongation. These results indicate that inhibition of replicon initiation is an important mechanism for the action of DNA-damaging agents in mammalian cells and strengthen the concept that control of DNA replication depends on the structural integrity of a chromosomal subunit that consists of several replicons.

¹ Supported by the U. S. Department of Energy.

Received 2/17/78. Accepted 9/ 8/78.

This article has been cited by other articles:

				P. Venkatesh, B. Shantala, G. C. Jagetia, K. K. Rao, and M. S. Baliga Modulation of Doxorubicin-Induced Genotoxicity by Aegle marmelos in Mouse Bone Marrow: A Micronucleus Study Integr Cancer Ther, March 1, 2007; 6(1): 42 - 53. [Abstract] [PDF]

				S. Kishi, N. Goto, T. Nakamura, and T. Ueda Evaluation of Cell-killing Effects of 1-{beta}-D-Arabinofuranosylcytosine and Daunorubicin by a New Computer-controlled in Vitro Pharmacokinetic Simulation System Cancer Res., June 1, 1999; 59(11): 2629 - 2634. [Abstract] [Full Text] [PDF]