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The Role of DNA Synthesis in Virus Replication and the Morphological Transformation of Normal Mouse Embryo Cells by MSV (MOLONEY)

Saskatchewan Research Unit of the National Cancer Institute of Canada, Saskatoon, Saskatchewan, Canada

Morphological transformation of normal mouse embryo cells by murine sarcoma virus (MOLONEY) and subsequent development of murine sarcoma virus growth were investigated using cytosine arabinoside (ara-C) and X-irradiation. Inhibition of DNA synthesis, cell division and transformation by ara-C were all reversible by deoxycytidine. The susceptibility of mouse embryo cells to infection and morphological transformation was most sensitive to ara-C during the first 6 hr after the virus-cell encounter. Sensitivity decreased with time, and by 24 to 48 hr virtually all infected cells had become transformed and completed the virus growth cycle, despite ara-C treatment. Irradiation of transformed, virus-producing cells with either 5000 R or 100,000 R had little effect on the ability of infected cells to produce murine sarcoma virus 24 hr later, and about 10% irradiated cells were still producing virus after 48 hr. Radiation survival and heat (37°) inactivation data for murine sarcoma virus (MOLONEY) are presented. The results indicate that the successful infection and morphological transformation of normal mouse embryo cells by murine sarcoma virus (MOLONEY) requires a DNA synthetic event immediately after the virus-cell encounter and, that once initiated, successful virus growth no longer depends on DNA synthesis.

Received 20 November 1969; accepted 11 February 1970.