Susceptibility to Transmitted Leukemia Occurring I N Pure Bred and Hybrid Mice'

Many investigators have called attention to the importance of heredity in breast cancer, lung tumors, leukemia, and other neoplasms of mice (cf. 1). Recently, the staff of the Roscoe B. Jackson Laboratory ( 2 ) has demonstrated the r61e of non-genetic factors and emphasized the need for a reinvestigation of the part played by heredity in the development of tumors.2 Experiments have been undertaken in this laboratory to determine the factors responsible for spontaneous leukemia and for susceptibility to transmissible leukemia. The studies on susceptibility to transmissible leukemia are described in this paper. The older literature concerning leukemia of mammals has been reviewed by Opie (3 ) . It is only within the past decade that the disease has been successfully transmitted in mice. Transmissible strains have been described by Korteweg (4), Richter and MacDowell ( 5 ) , Mercier and Gosselin ( 6 ) , Krebs, Rask-Nielsen and Wagner ( 7 ) , Dobrovolskai'a-Zavadskai'a (8), Lawrence and Gardner ( 9 ) , Lewis (lo), and workers in this laboratory (11). There are few reports on the heredity of transmissible leukemia. The most extensive of these is that by MacDowell and Richter ( 1 2 ) . Other workers have given only fragmentary data, MacDowell and Richter inoculated cells of their Line 1, originating in the highly leukemic stock C58, into other mice of the same stock, into mice of the Storrs-Little stock, which had no previous history of leukemia, and into first and second generation hybrids ( F1 and Fp) and back-cross combinations. These cells failed to grow in Storrs-Little mice but produced leukemia in almost every mouse of the C58 stock and of the first hybrid generation. The frequency of the disease among other hybrid combinations, including back-crosses, suggested that a single dominant gene was responsible for susceptibility. Cells from another C58 mouse (Line A) gave somewhat different results in hybrid combinations. The percentages of susceptible mice were much smaller and variable. The ratios of susceptible to resistant mice observed in back-cross generations suggested that from two to seven genes might be operating. On the basis of genetic studies of spontaneous leukemias MacDowell and Richter (13 ) concluded that a semi-dominant gene determined the incidence of the disease. Slye ( 14), however, believes that her results are best explained by assuming a single recessive gene responsible for the occurrence of leukemia and an additional localization factor.