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Complexity and Abundance of Murine Leukemia Virus-related Nuclear and Messenger RNA Sequences in Mouse Embryo Cell Lines Which Are Differentially Sensitive to Carcinogen-induced Virus Activation¹

Department of Pathology and Anatomy, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55901

The abundance and diversity of endogenous murine leukemia virus (MuLV)-related nuclear and messenger RNA sequences have been studied in two different lines of mouse embryo cells in culture. AKR-2B cells, derived from high-leukemia-incidence mice readily undergo activation of endogenous virus production when transformed by chemical carcinogens. C3H/10T cells, derived from low-tumor-incidence mice, do not activative virus production when transformed by chemicals. Evidence is presented to suggest that this differential inducibility of virus production by carcinogens may be related to the stringency of cellular control over the transcription of MuLV-related genes in these two cell lines. Steady state nuclear RNA from both non-virus-producing AKR-2B cells and that of a chemically transformed, virus-producing derivative (AKR-MCA) appears to contain AKR-MuLV-related RNA sequences of equivalent complexity as assayed by molecular hybridization using a representative complementary DNA probe. The relative abundance of such sequences, however, is much greater in the chemically transformed clone. Polyribosome-associated, ethylenediaminetetraacetate-released messenger RNA from AKR-2B cells contains MuLV-related sequences of lower complexity than that found in the nucleus of the same cells. These sequences appear to be of lower molecular weight than the nuclear sequences and contain only about 50% or less of the MuLV genomic complexity. Thus, chemically transformed AKR cells exhibit a large increase in the abundance of MuLV-related nuclear RNA sequences but with no detectable change in the complexity, whereas changes in both the complexity and abundance are readily apparent in polyribosome-associated messenger RNA. In contrast, C3H/10T cells contain nuclear and polysomal MuLV-related RNA sequences of similar complexity. The complexity of these sequences is less than the MuLV complexity, and no posttranscriptional regulation is apparent.

¹ This work was supported by Grant CA 16816 from the National Cancer Institute, Department of Health, Education and Welfare, and by the Mayo Foundation.

² To whom requests for reprints should be addressed.

Received 8/ 7/78. Accepted 10/20/78.