Acute Hepatic Manifestations following Treatment with Urethane or Methyli~ormamide*

Several workers have observed the incidental occurrence of a viral disease in various strains of transplantable leukemias in mice. Nelson (1-4) has fully described a filterable agent causing acute hepatitis in leukemic mice of the Princeton strain. Although he made repeated efforts to keep the leukemia in passage, it was regularly lost after a few transfers. Marked pathological changes were noted in the livers of some of the mice which died, and a filterable agent capable of inducing similar changes was obtained from the liver. A disease closely related to that described by Nelson had been found by Gledhill and Andrewes (5, 6) in the Webster strain of VS mice, following the injection of liver filtrates from the Parks strain of mice. Later, it was discovered that the full expression of the disease was determined by the presence of Eperythrozoon coccoides (7). This finding was subsequently confirmed by Nelson (4), who showed that the virulence of the hepatitis virus in Swiss mice--which have a high natural resistance to infection by the agent,--was greatly enhanced by combined infection with the eperythrozoon. MacDowell eta/. (8) had also reported the presence of a virus in line I leukemia that caused a mild illness in C58 mice in which the line was carried, but was fatal to Bagg albino mice in which the leukemia did not "take." Somewhat similar diseases caused by filterable agents were noted by De Bruyn (9) in animals bearing a transplantable lymphoma and by Law and Dunn (10) in a subline of transplantable lymphatic leukemia L 1210 in dba mice. Although these workers (8-10) did not specifically refer to a ,hepatitis, the signs and symptoms they described are strikingly similar to our findings.