Journal of Experimental Medicine, Vol 144, 1406-1423, Copyright © 1976 by Rockefeller University Press
Radiation leukemia in C57BL/6 mice. II. Lack of ecotropic virus expression in the majority of lymphomas
JN Ihle, DR Joseph and NH Pazmino
The expression of endogenous ecotropic viruses in radiation-induced
thymomas of C57BL/6 mice was examined. Competition radioimmunoassays for
AKR MuLV gp71, p30, and p12 were used for viral antigen expression. 3 of 40
lymphomas had readily detectable ecotropic gp71 at levels of 95- 689 ng/mg
protein; the remainder of the tumors had no detectable gp71 (less than 1.0
ng/mg protein). 30 thymomas were characterized by the presence of MuLV p30
at levels of 1-10 ng/mg protein, levels that were comparable to those found
in thymus extracts from age-matched, nonirradiated control. 10 tumors were
characterized by having p30 levels of 10-30 ng/mg protein. In one tumor
significant levels of AKR MuLV p12 were detectable. Since B-tropic and
N-tropic viruses from C57BL/6 mice have glycoproteins (gp71)
indistinguishable from AKR MuLV gp71 and the N-tropic virus had a p12
serologically identical to AKR MuLV p12, these results demonstrate that
overt endogenous B-tropic virus was detectable in 2 of 40 thymomas and
endogenous N-tropic virus was detectable in 1 of 40 thymomas. The lack of
overt expression of gp71 or p12 was also confirmed by cytotoxicity assays
using monospecific antisera to these viral proteins. Radiation-induced
lymphomas were also examined for the presence of reverse transcriptase
after chromatography of tissue extracts on poly G-Sepharose. One tumor,
which was characterized by the lack of gp71, also had no detectable reverse
transcriptase; whereas one tumor with gp71 was characterized by readily
detectable levels of reverse transcriptase in cellular extracts. The
presence of viral RNA was examined using AKR cDNA. Low levels of RNA
capable of hybridizing with AKR cDNA were found in age- matched,
nonirradiated mice; these hybrids had Tm's of 72 degrees C, while hybrids
with AKR MuLV 70S RNA had Tm's of 80 degrees C. In 1 of 12 thymomas the
concentration of hybridizable RNA and the Tm of the hybrids were identical
to control values. In 9 of 12 thymomas the concentration of hybridizable
sequences increased approximately three- to fivefold and the Tm of these
hybrids varied from 73 to 75 degrees C. In 1 of 12 thymomas the
concentration of hybridizable sequences increased over 100-fold, hybridized
completely with AKR MuLV cDNA, and the hybrids had Tm's of 79 degrees C.
This thymoma was also characterized by the presence of the AKR MuLV type of
gp71 and p12. One tumor was characterized by a 10-to 100-fold increase in
hybridizable sequences, which only partially hybridized with AKR MuLV cDNA,
and hybrids had a Tm of 73 degrees C. This tumor was characterized by the
presence of AKR MuLV gp71 but not AKR MuLV p12. The results taken together
demonstrate that overt endogenous ecotropic virus expression is only rarely
detectable in radiation-induced thymomas of C57BL/6 mice.
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