Repeated Demonstration of a Mouse Leukemia Virus After Treatment With Chemical Carcinogens2

Abstract

A single, neonatal injection of 7,12-dimethylbenz[a]anthracene (DMBA) into mice increased the level of detectable leukemogenic activity in various tissues assayed at short intervals after treatment as well as in primary tumors. This activity was demonstrated by the injection of extracts of the tissues or tumors directly into the thymus of a newborn mouse or into intrarenal thymic grafts prepared as described by Haran-Ghera et al., Cancer Research 26: 438–442, 1966. Of 11 DMBA-induced thymic lymphomas tested, 9 gave positive results; 2 transplanted DMBA-induced thymic lymphomas were positive, 4 were not. The third serial animal passage of a preparation derived from one of the positive thymic lymphomas produced tumors in 56 of 92 animals. The average time for tumors to reach approximately 15 × 20 mm was 68 days. Serial animal passage of cell-free filtrates from primary lymphomas behaved similarly. Cell-free extracts from liver and bone marrow taken 3–7 days after neonatal administration of DMBA (but not from untreated animals) also contained leukemogenic activity that was also enhanced by serial animal passage. A lymphoma arising on the third serial animal passage yielded a cell-free filtrate that could rescue the MSV genome present in Moloney sarcoma virus-induced hamster tumor cells (non-producer, genome carrier). Also, mouse-embryo cell cultures infected with the same filtrate produced syncytia when cocultured with tissue culture cells of the XC cell line (Rous virus-induced rat tumor). In addition, 3 DMBA-induced primary fibrosarcomas and 1 methylcholanthrene-induced fibrosarcoma yielded a 10,000 × g tumor cell supernatant (irradiated with 20,000 rad) which induced thymic lymphomas when injected into intrarenal thymus grafts.