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An Electron Microscopic Study of Leukemia Induced in Rats with Gross Virus^*

( Columbia University, Francis Delafield Hospital, Department of Pathology, New York, New York)

The leukemia virus of Gross was adapted to W/Fu rats to which it became as highly pathogenic as to mice. The lymphomas produced in rats were invariably thymic with or without leukemia and involvement of other organs.

An electron microscopic study was made of abundance of virus in the blood and various organs. Virus was found most often (100 per cent) and in greatest abundance in the thymus. The earliest clearly recognizable change was "budding" on the plasma membrane associated with accumulation of virus between well preserved cells. At an advanced stage of the disease, cytopathic changes were evidenced by dissolution of the plasma membrane innumerable viral particles intermingling with mitochondria, and other cytoplasmic elements.

Intracellular viral particles were abundant in vesicles or canals and specific granules of megakaryocytes of the spleen and bone marrow, and few elsewhere in their cytoplasm. Conventional electron micrographs give no clue as to the primary site and mode of replication of viral nucleic acids.

The viral particles seen resembled those of other leukemias. Some possessed tail-like structures as first described by Dalton for the Moloney virus (3, 4).

By fractionation of the blood plasma a nearly pure preparation of viral particles was obtained. This procedure was adapted to the thymus by dissociation of thymic cells by treatment with trypsin (instead of homogenization), followed by fractional centrifugation.

The abundance of virus and the neoplastic transformation of lymphocytes in the thymus may be related to the presence of a specific factor in this organ.

^* This work was supported by Grant C-A06215-03 of the National Cancer Institute.

Received 4/24/63.