Common proviral integration sites in C57BL mouse lymphomas induced by radiation leukemia virus and absence of novel virus-related sequences in radiogenic lymphoma DNA.
Three C57BL/Ka mice were inoculated with RadLV/VL3, a thymotropic and leukemogenic virus population released by the permanent BL/VL3 cell line, which was derived from a C57BL/Ka lymphoma induced by radiation leukemia virus (RadLV). The neoplastic thymus and bone marrow cells from these mice were grown until the cultures became permanently established, and their DNAs were examined for the presence of virus-related sequences by restriction enzyme analysis. All six cell lines displayed identical EcoRI and BamHI restriction fragments, not found in control C57BL/Ka DNA and accounting for the presence of more than one novel provirus. The primary and secondary tumors were thus clonal and, even though they were obtained from different animals, possessed identical integration sites. The BL/VL3 cell line also displayed the clonal appearance of novel proviral sequences, partly identical, with respect to location and BamHI restriction pattern, to those found in the RadL/VL3-induced tumor cell lines. Neither radiation-induced tumors, nor cloned cell lines derived therefrom, whether producing leukemogenic virus (BL/RL12-P) or not (BL/RL12-NP), displayed the presence of novel virus-related sequences when compared with control tissues. Our results strongly suggest not only that, as described in the case of avian leukosis virus-induced tumors of the chicken, RadLV-induced leukemogenesis might be a consequence of cellular gene activation by promotor insertion, but also that more than one integration site might be involved. Radiation-induced tumorigenesis might be initiated by a comparable mechanism, not requiring the participation of a virus.
D000818:Animals; D001287:Attachment Sites, Microbiological; D002460:Cell Line; D002472:Cell Transformation, Viral; D004251:DNA Transposable Elements; D004273:DNA, Neoplasm; D004587:Electrophoresis, Agar Gel; D005814:Genes, Viral; D009052:Leukemia Virus, Murine / Q000235:genetics*; D008223:Lymphoma / Q000382:microbiology*; D008242:Lysogeny; D051379:Mice; D008810:Mice, Inbred C57BL; D009381:Neoplasms, Radiation-Induced / Q000382:microbiology*; D014412:Tumor Virus Infections / Q000382:microbiology
D004251:DNA Transposable Elements; D004273:DNA, Neoplasm