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J Virol. 1970 December; 6(6): 738-749
Copyright © 1970 American Society for Microbiology. All Rights Reserved.

Changes in Deoxyribonucleic Acid Synthesis Regulation in Chinese Hamster Cells Infected with Simian Virus 40 ¹

The Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104

ABSTRACT

Infection of primary or secondary cultures of Chinese hamster embryo cells with simian virus 40 at a multiplicity of 20 to 50 induced synthesis of the virus-specific intranuclear T antigen in 80 to 90% of the cells within 48 to 72 hr. In the infected cultures, 30 to 50% more cells were recruited into deoxyribonucleic acid (DNA) synthesis than in the controls, whether or not the cultures were confluent. The newly synthesized DNA was mostly cellular, since little virus was produced (as shown by various techniques: immunofluorescence for viral antigen, virus growth curves, and isolation of viral DNA from infected cultures). Transformed cells could be detected a few weeks after infection and produced tumors when inoculated into irradiated animals. Chromosomal changes were observed soon after infection (24 hr). Initially, there was a marked increase in the proportion of polyploid cells (8 to 14%), most of which were chromosomally normal. In a few weeks, a large majority of the infected population was polyploid (30 to 50%). Thus, the polyploid cells have the ability to proliferate. Evidence is presented to suggest that polyploid cells arise by stimulation of cells in the G₁, G₂, or S phases to undergo two or more successive periods of DNA synthesis without an intervening mitosis. With a subsequent loss or redistribution of chromosomal material, this may lead eventually to a biologically transformed cell; thus, it is suggested that the initial event(s) relevant to transformation occurs at the level of control of cellular DNA synthesis.

² Present address: Department of Pathology, University of Colorado Medical School, Denver, Colo. 80220.

³ Department of Pathology, School of Medicine, University of Pennsylvania. Recipient of Faculty Research Award PRA-47 from the American Cancer Society.

¹ Submitted by John M. Lehman in partial fulfillment of the requirements for the Ph.D. degree to the Department of Pathology, University of Pennsylvania, Philadelphia.