Metabolic Alteration in Leukæmia induced by a Virus

Abstract

RECENT publications^1,2 reporting the induction of leukæmia in mice by cell-free extracts have reawakened general interest in the role of viruses as oncogenic agents and, as a corollary, in the metabolic alterations induced by these agents. It has been shown in this laboratory that alterations in host cell metabolism induced by virus can be detected very soon after infection³. The current investigation was undertaken to see if analogous effects could be observed in vivo using one of the viruses inducing tumours. The agent investigated here was that described by Friend² as producing a Leukæmia in mice, characterized by splenomegaly and an accumulation in the spleen of stem cells. The basic experiments were performed as follows: 150 mice were infected i.v. with 0.2 ml. of a cell-free filtrate from spleens of mice carrying the infection. 150 control mice received the same amount of cell-free filtrate prepared from normal spleen. Beginning the day after inoculation of the virus, and at the intervals thereafter indicated in Fig. 1, six infected and six control mice were selected at random and given intraperitoneal injection of 5 µc. of phosphorus-32. 3 hr. later the spleens of these animals were removed, weighed, dried in pre-weighed planchets, reweighed, the radioactivity determined, and expressed as c.p.m./mgm. dry tissue. The averaged wet-weights of the spleens from a typical experiment as well as the averaged c.p.m./mgm. dry spleen are given in Fig. 1. As part of the same experiment, on the fifth day some of the control and the infected mice received 300 r. of total body X-irradiation. The results for weight and radioactivity of the spleens of these mice examined on subsequent days are also included in Fig. 1.