Strong selection for cells containing new ecotropic recombinant murine leukemia virus provirus after propagation of C57BL/6 radiation-induced thymoma cells in vitro or in vivo.

Abstract

Using the Southern procedure, we have studied the presence of ecotropicspecific murine leukemia viral sequences in genomic DNA isolated from primary X-ray-induced thymomas, from lymphoid cell lines established from them, or from secondary tumors passaged in vivo. We found that primary radiation-induced thymomas and infiltrated spleens do not harbor newly acquired ecotropic provirus. However, additional ecotropic proviruses (which appear recombinant in the gagpol region) could be detected in most of the tumorigenic cell lines established in vitro from them and in tumors arising from subcutaneous transplantation of the primary thymomas. These results suggest that primary radiation-induced thymomas may not be clonal. They also indicate a strong correlation between the presence of ecotropic recombinant proviruses in the genome and the growth ability, both in vitro and in vivo, of specific cells within these thymomas, suggesting a possible mitogenic function for murine leukemia virus.

Amplification of endogenous proviral MuLV sequences in radiationinduced osteosarcomas

“…This result is in contrast to X-ray-induced radiation leukemias in BALB/c mice, where the majority of-tumors lacked newly acquired ecotropic proviruses (Jolicoeur et al, 1983;Newcomb et al, 1985). Although the data were obtained from transplants rather than from primary tumors, we show evidence that the reintegrations of proviruses are not due to a transplantation effect as has been suggested in the case of radiation-induced thymomas (Jolicoeur et al, 1983). The situation in radiation-induced osteosarcomagenesis seems to be different for the following reasons.…”

“…This approach of searching for newly tion with an excess of the indicated restriction endonuclease. acquired proviruses in tumor tissue has also been used to The DNA fragments were separated on 0.8% agarose gels, elucidate the role of endogenous retroviruses in spontaneous transferred to nitrocellulose filters (Southern, 1975), and hyand induced leukemias in mice (Jolicoeur et al, 1983).…”

Monoclonal proliferation of Friend murine leukemia virus-transformed myeloblastic cells occurs early in the leukemogenic process.

“…Our results are in contrast to the results reported by Jolicoeur et al (15) for radiation-induced leukemias; in that study, in vitro or in vivo passages of primary tumors were always associated with a monoclonal selection characterized by reintegration of ecotropic viral sequences. In fact, in vitro or in vivo passages of F-MuLV-induced primary myeloid leukemias are usually not associated with monoclonal selection as long as integrated F-MuLV copies are considered (data not shown).…”

Induction of thymic lymphosarcomas in C57BL/6 mice after inoculation of weakly oncògenic viruses associated with a sub‐leukemogenic radiation exposure (1.75 GY × 2)

“…The presence of leukemogenic RNA viruses in cellfree extracts of radiation-induced thymic lymphosarcomas (TL) has been demonstrated in C3H mice (Gross, 1959) and in the C57BL/Ka strain (Lieberman and Kaplan, 1959). These findings were later confirmed (Latarjet and Duplan, 1962;Haran-Ghera, 1966) suggesting that a viral agent may account for the fundamental observation that TL may develop from a non-irradiated thymus engrafted into previously thymectomized and irradiated recipients (Kaplan and Brown, 1954). Thus, X-rays would result in the activation of endogenous N-ecotropic and xenotropic retroviruses and favor the emergence of B-ecotropic leukemogenic recombinant viruses (Benade and Ihle, 1980).…”

“…The first considers that viruses are not causative agents of TL; actually those tumors would result from a durable overstimulation of thymic cells secondary to the simultaneous depletion of the lymphoid system and of the progenitor cell pool occurring after fractionated radiation exposure. This mechanism was originally envisaged to explain the malignant transformation of non-irradiated thymuses engrafted into previously thymectomized and irradiated recipients (Kaplan and Brown, 1954;Kaplan et al, 1956). The second possibility is that the DNA copies of radiation-derepressed viruses-which need not be oncogenic per se-might activate cellular oncogenes when their promoter and enhancer sequences were inserted close to critical points of the cellular genome.…”