Alteration of biologic behavior of a rat leukemia by different routes of passage

Two clonal leukemia cell lines exhibiting diploidy or tetraploidy were isolated separately from a mother cell population of rat myelogenous leukemia DBLA-6 (induced by 1-butyl-1-nitrosourea), and their biologic characteristics altered during serial iv or ip passages in Donryu rats were examined. In early generations after the establishment of the clones, leukemia-inducing capacities were clearly demonstrated only in the diploid clone and were characterized as follows: a) release of leukemia cells into the peripheral blood after inoculation, and b) infiltration, and growth of leukemia cells in the bone marrow and spleen. After repeated iv passages, however, leukemia-inducing capacity was greater not only in the diploid but also in the tetraploid clone. By serial ip passages, this capacity was never acquired but was gradually lost even in the diploid clone. Cell electrophoretic mobility, cell size, or susceptibility to chemotherapeutic agents were also modified. There was a strong correlation between the routes of passage and the direction of the changes: The iv route enhanced or the ip route suppressed the leukemia-inducing capacity. Chromosome constitutions were also changed.