Selection for virulence and organ-specific metastasis of herpesvirus-transformed lymphoma cells.

The Marek's Disease virus-transformed, non-producer, lymphoma cell line, MDCC-RPI, was selected by sequential transplantation to produce a highly malignant variant, MDCC-ALI. This is evidenced gy an 18-fold decrease in LD50. The new cell line has an increased ability to form metastatic lesions in a distribution which mimics the natural disease. Further selections for organ-specific metastasis were undertaken with the isolation of two cell lines, MDCC-AL2, selected for liver metastasis, and MDCC-AL3, selected for ovary metastasis. In vivo studies show that the selection was unsuccessful in the case of the ovary but successful in the case of the liver. Two assays were developed, utilizing the chick embryo and intravenous injection of lymphoma variants. One measures liver-specific metastasis by the enumeration of tumor foci on the embryonic liver. The second, chorioallantoic membrane (CAM) focus formation, correlates with the virulence of the injected lymphoma cells. The liver-selected tumour variant cells form more liver foci than any other tumour variant cells. The genetic background of the embryo does not affect formation of liver foci. Resistance to CAM focus formation correlates with major histocompatibility complex associated resistance to MD.