Lack of ecotropic virus involvement in induction of lymphomas in DBA/2J mice by 7,12-dimethylbenz(a)anthracene.
DBA/2 mice carry a single endogenous ecotropic murine leukemia provirus, Emv-3, that is replication defective because of a single nucleotide substitution in codon 3 of p15gag. However, when weanling DBA/2 mice are treated percutaneously with 7,12-dimethylbenz(a)anthracene (DMBA), ecotropic virus replication is induced in almost all of the treated mice. Previous studies have shown that this induction results from DMBA-induced reverse mutations in codon 3 that allow efficient virus replication. In addition to ecotropic virus replication, DMBA also induces lymphomas in 100% of the treated mice. These results have raised the possibility that ecotropic virus replication is causally associated with the development of lymphomas in DBA/2 mice, perhaps via the insertional activation or mutation of cellular proto-oncogenes. To test this possibility, we compared lymphoma incidence after percutaneous DMBA treatment in DBA/2J-dv/dv mice, which carry two copies of Emv-3, with lymphoma incidence in DBA/2J-d+18J/d+18J mice, which lost both copies of Emv-3 by homologous recombination involving the long terminal repeat sequences. The results of this study conclusively demonstrated that Emv-3 is not causally associated with the development of DMBA-induced lymphomas in DBA/2J mice. Interestingly, histopathological and molecular analyses of the lymphomas indicated that the majority of the lymphomas in both strains of mice were of the B-cell lineage. This was unanticipated, since the majority of chemically induced lymphomas in other inbred strains are thymic lymphomas, presumably of the T-cell lineage. Thus, DBA/2 mice appear to present a unique model system for the investigation of chemically induced B-cell lymphomas in mice.
Mercer
J A
JA
Mammalian Genetics Laboratory, National Cancer Institute Frederick Cancer Research Facility, Maryland 21701.
Jenkins
N A
NA
Copeland
N G
NG
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D003673:Defective Viruses / Q000235:genetics* / Q000502:physiology; D015321:Gene Rearrangement; D015329:Gene Rearrangement, T-Lymphocyte; D005803:Genes, Immunoglobulin; D009052:Leukemia Virus, Murine / Q000235:genetics* / Q000502:physiology; D008223:Lymphoma / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D008811:Mice, Inbred DBA; D014779:Virus Replication
D015127:9,10-Dimethyl-1,2-benzanthracene