For the ICRF Annual Report, 1979: I. The Rare Revertants of an ASV-Transformed Rat Cell Have Lost Proviral DNA or Bear Mutations
Varmus here provided an overview of his research during his sabbatical year at the Imperial Cancer Research Fund in London
in 1978-79. His studies focused on the ways in which retroviruses cause mutations of genes, including the genes deposited
by other retroviruses that had previously infected the cell.
Item is a photocopy.
Number of Image Pages:
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Original Repository: University of California, San Francisco. Archives and Special Collections. Harold E. Varmus Papers
Reproduced with permission of the Regents of the University of California.
Medical Subject Headings (MeSH):
Avian Sarcoma Viruses
Retroviruses and the Genetic Origins of Cancer, 1970-1993
Letter from Harold Varmus to Howard Young, National Cancer Institute (August 28, 1979)
For the ICRF Annual Report, 1979: II. Retroviruses as Mutagens: Isolation of Revertants with Deletions and/or Insertions in
the ASV Provirus in B31 Cells after Superinfection with MuLV (1979)
For the ICRF Annual Report, 1979: III. Co-Transfection with Papovavirus and Retrovirus DNA Using Recombinant DNA Prepared
In vitro (1979)
The molecular events responsible for reversion of cells from a transformed to a normal phenotype may provide important clues
to an understanding of oncogenesis and its control. We have isolated and characterized spontaneous revertants of a clonal
line of rat-1 cells transformed by the B77 strain of avian sarcoma virus (ASV). This cell line (B31) carries a single, normal
ASV provirus, yields wild type ASV efficiently upon fusion with chicken cells, and has an extremely stable transformed phenotype.
Using selective procedures to kill transformed cells, we have isolated subclones of B31 which have morphological and growth
properties of uninfected rat-1 cells (revertants); these are present in the B31 cultures at a frequency of about 10^-4 to
The revertants have been found to fall into two classes. (i) About one-fourth of the revertants have lost the entire ASV
provirus, as demonstrated by hybridization to restriction endonuclease digests of cellular DNA; the mechanism by which the
provirus was lost is not known. (ii) The other revertants have acquired mutations in the viral gene (src) required for transformation:
they retain a normal provirus; contain the usual species of viral RNA at the same concentrations as in B31 cells (tests performed
by N. Quintrell, University of California, San Francisco, [UCSF]); can be retransformed with ASV; yield non-conditional, transformation-defective
mutants after fusion with chicken cells; and encode products of scr which are abnormal in stability, structure, immunoreactivity,
and/or protein kinase activity (done in collaboration with H. Oppermann and A. Levinson, UCSF). In some cases, reversion
of the src mutations to wild type occurs at low frequency as manifest by spontaneous retransformation of the rat cells or
by recovery of transforming virus during propagation of the mutant viruses in chicken cells. The independence of the mutations
has been documented by recovery of wild type recombinant viruses after mixed infections of chicken cells with pairs of mutant
viruses. Detailed analysis of about 30 such src mutations and their aberrant products is underway in collaboration with Drs.
Oppermann and Levinson.