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Virus Morphogenesis in a Mouse Lymphoma¹

Department of Anatomy, Yale University School of Medicine, New Haven, Connecticut 06510

A primary pituitary tumor (PPT) developed in one of four isologous pituitary glands that were transplanted s.c. in a hybrid mouse (C57 x BALB/c). The mammary glands of the host were thick and lactating; its spleen and liver were enlarged; and the lower uterine horns and the cervix were also enlarged, firm, and fibrous. The PPT was transplanted s.c. in isologous hosts, six female and six male, and 170 to 190 days later, five female and two male hosts had transplanted pituitary tumors and five female and six male hosts had ascites and generalized lymphoma. In the subsequent transfer generations, the mice bearing transplants survived only 4 weeks or less. The PPT grew at the site of transplantation and also involved remote nodes and the liver and the spleen. The tumor after the first transfer contained medium and large lymphoblastic cells with multiple nucleoli and mitotic figures. Examination by electron microscopy revealed virus-like particles in juxtaposition to chromatin and within the rough endoplasmic reticulum (ER) surrounding the nucleus. Morphogenically, the ribosomes successively aggregated and fused on the ER membrane to form long and short osmiophilic bars that bulged into the ER cisternae and then separated to form viral particles (VP's) of the C-type (oncorna- or leukoviruses) measuring about 100 nm in diameter. VP's were not found outside the ER. The distribution of RNA and DNA in the nuclei and cytoplasm of the lymphoma cells was revealed by the acriflavine-phosphotungstate technique. The provirus bars and the VP's were electron opaque after RNase treatment and slightly less dense after DNase treatment. Only the protein capsids remained after incubation with both DNase and RNase.

¹ This study was supported by the USPHS Research Grant CA 00343 from the National Cancer Institute.

Received 3/ 2/73. Accepted 11/ 6/73.