New Class of Leukemogenic Ecotropic Recombinant Murine Leukemia Virus Isolated from Radiation-Induced Thymomas of C57BL/6 Mice

Abstract

We previously reported the establishment of several lymphoid cell lines from Xray-induced thymomas of C57BL/Ka mice, and all, except one, produce retroviruses (P. Sankar-Mistry and P. Jolicoeur, J. Virol.35:270-275, 1980). Biological characterization offive of these new primary radiation leukemia viruses (RadLVs) indicated that they had a B-tropic, fibrotropic, and ecotropic host range and were leukemogenic when reinjected into C57BL/Ka newborn mice. The leukemogenic potential of one isolate (G6T2) was further assessed and shown to be retained after prolonged passaging on fibroblasts in vitro. Restriction endonuclease analysis of the DNA of four of our new RadLV isolates (G6T2, Ti-7, Ti-8, and Ti-9) revealed

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)

“…This result is consistent with the observation of Rassart that XCf B-tropic MuLV can frequently be re-covered from lymphoid cell lines established from primary radio-induced TL (Rassart et al, 1983). The genome of C57BL/6 mice harbors one copy of the endogenous ecotropic retrovirus (Jolicoeur et al, 1983).…”

“…The B-ecotropic viruses used in the preceding experiments belong to a group of viral recombinants which are commonly recovered from tissues of old C57BL/6 mice (Odaka, 1975;Benade et al, 1974) and of mice submitted to radioleukemogenic protocols Lieberman et al, 1979;Sankar-Mistry and Jolicoeur, 1980) as well as from in vivo-and in vitropassaged TL (Rassart et al, 1983). These viruses are considered as non-leukemogenic or weakly leukemogenic because they seldom produce TL when injected i.p., although they induce a high frequency of nonthymic B lymphomas after latency periods always exceeding 400 days (Legrand et al, 1982).…”

“…Irrespective of the protocol, an additional copy of a recombinant which is likely to correspond to 1223 was integrated in the genomic DNA of all tumors passaged in vivo. Novel recombinant MuLV sequences were also detected in a few in vivo-and in vitropassaged tumors derived from virus-negative primary radio-induced tumors (Jolicoeur et al, 1983) whereas no such sequences were detected in either primary or in vitro-passaged tumors (Janowski et al, 1982).…”

“…In the control liver DNA of C57BL/6 mice, this probe detected a 4.0 KpnI fragment (Fig. 2, lane 1) corresponding to the single endogenous ecotropic MuLV DNA (Jolicoeur et al, 1983). The 1223 virus, like other B-ecotropic recombinant viruses isolated from C57BL mice, have an additional KpnI site in their genome (Janowski et al, 1982;Kim et al, 1982; @<O.ool).…”

“…When mice were treated by protocol 2, virus was detected in 5 mice out of 18: the xc test was positive for thymus (3 mice) for thymus and BM (1 mouse), and for thymus, BM and spleen (1 mouse). The differ-tected either in thymus and BM (5 mice) Or in thymus, Rassart et al, 1983). Thus, a 3.5-Kbp internal KpnI fragment is recognized by the env ecotropic probe.…”