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Biological and Morphological Studies of SJL/J Strain Reticulum Cell Neoplasms Induced and Transmitted Serially in Low-Leukemia-Strain Mice¹

Department of Virology, The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston, Texas Medical Center, Houston, Texas 77025

Reticulum cell neoplasms (RCN) were induced in 4 of 34 BALB/c low-leukemia-strain mice inoculated i.p. with supernatants of centrifuged extracts of spontaneous reticulum cell sarcomas of SJL/J strain mice. The extracts were obtained from tumorous organs and from tumorous spleen tissue culture derived from SJL/J strain mice. The RCN's induced in BALB/c mice were transmitted serially to other low-leukemia-strain mice (BALB/c, C3H/f, and C3HeB/FeJ) by similarly prepared cell extracts and by cell-free filtrates of tumorous organs of the mice. The lesions induced included RCN types A and B (Dunn's nomenclature) and heterotopic myelopoiesis, including some cases which histologically could be described as myeloid and erythroid leukemias and megakarocytosis. The incidence of induced RCN in mice increased to 92%, and the average latent period decreased to 90 days as serial transmission of the RCN progressed.

Electron microscopic examination of lymph nodes, spleen, thymus gland, liver, kidneys, lungs, and bone marrow of mice with induced RCN revealed varying numbers of virus particles irrespective of the histological type of lesions. The virus particles were morphologically identical with murine leukemia type C virus particles and with virus particles observed in spontaneous RCN of SJL/J strain mice. Budding particles were observed in cells of all organs examined. Intracisternal type A virus particles were found in some organs. Type C virus particles were observed in cells of all examined tissue culture passages of tumorous spleen derived from an SJL/J strain mouse with spontaneous RCN. Budding virus particles were also observed in tissue culture, indicating that the particles multiply for prolonged periods in vitro. Biological activity of the virus produced in vitro was demonstrated by induction of RCN in BALB/c strain mice inoculated with supernatants from a centrifuged extract of tissue culture cells. Tissue culture from embryos of an apparently normal SJL/J strain mouse also contained type C virus particles. This indicates vertical transmission of the virus in mice of this strain.

The observation of type C murine leukemia virus particles in organs of the low-leukemia-strain mice with induced RCN and myeloproliferative lesions and in tissue cultures of spontaneous RCN derived from SJL/J strain mice and the serial transmission of induced RCN by cell-free filtrate strongly support viral etiology of this type of neoplasia.

¹ Presented at the 26th Annual Meeting of the Electron Microscope Society of America, New Orleans, La., September 16 to 19, 1968. This study was conducted under Contract PH43-65-604 (awarded to L.D.) within the Special Virus Cancer Program of the National Cancer Institute, NIH, USPHS.

² Visiting Associate Professor of Virology, The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston, and Visiting Associate Professor of Chronic Diseases, The University of Texas School of Public Health, Houston, Tex.

Received 6/17/69. Accepted 8/11/69.

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