Adverse effects of mouse hepatitis virus on ascites myeloma passage in the BALB/eJ mouse

Abstract

During experimental serial passage of ascites myelomas through BALB/cJ mice, unexpected illness and premature deaths occurred. Postmortem examination of affected mice revealed focal or diffuse discolored depressed areas in the liver and, in some cases, splenomegaly. Histopathologic findings consisted of focal to diffuse areas of necrosis with minimal leukocytic infiltration. Aerobic and anaerobic bacterial cultures of livers and spleens from affected mice were negative. Mouse hepatitis virus (MHV) was isolated from livers of clinically ill mice and from the ascites myeloma lines. An MHV contaminated ascites myeloma line, when passed into nude (nu/nu) mice, killed the animals in 6 days; the virus was isolated from livers of inoculated mice. Attempts to determine the source of the infection were unsuccessful. Serologic survey of newly acquired mice indicated no evidence of antibodies to MHV while mice in holding rooms had titers that ranged from 1:10 to 1:40. Two solid myeloma lines (being maintained by subcutaneous passage) were negative for MHV when tested by virus isolation techniques, and nine lines were negative to 11 murine viruses when tested by mouse antibody production assay. Attempts to demonstrate Eperythrozoon coccoides in control BALB/cJ mice were unsuccessful. Because of the outbreak, changes were made in animal handling procedures. A colony of BALB/cAn mice negative to MHV antibodies was established to provide animals for experimental passage of tumors, and animals in both the breeding and transfer room were placed under filter tops. The results were encouraging. In the four newly established tumor lines, one having been passed 46 times, no illness or unexplained deaths were observed.