Tumorigenicity testing of various cell substrates for production of biologicals

The data presented in this paper confirm earlier findings that the antithymocyte globulin (ATG) treated newborn Wistar rat is more sensitive than the nude mouse in allowing the metastatic potential of a cell substrate to be displayed. Several human neoplastic cell lines such as HeLa, FL, Hep-2, KB and WiDr cells as well as monkey kidney cell lines such as Vero and BSC-1 cells, which failed to metastasize in nude mice, formed metastases in ATG-treated newborn rats. Earlier studies on the tumorigenicity of Vero monkey kidney cells were extended to various passage levels of BSC-1 aneuploid and CV-1 diploid monkey kidney cells in order to establish the effect of prolonged in vitro culture on the oncogenic potential of African green monkey kidney cells. It was found that BSC-1 and CV-1 cells--like Vero cells--showed increased tumorigenicity in the rat model with increasing cell passage. Cells of all three cell lines passaged 146 to 257 times formed invasive adenocarcinomas in the muscle (inoculation site) of the animals. Considering the passage levels, at which the adenocarcinomas appeared and lung metastases were detected, the malignant potential was most pronounced in CV-1 cells, followed by Vero cells and was lowest in BSC-1 cells. Results obtained from the in vitro tumorigenicity assay of cell colony formation in soft agar confirmed the rat test results: increased cell passage of all three monkey kidney cell lines resulted in higher cell colony formation. The in vitro chick embryo skin culture assay was found unsuitable for the differentiation of various passage levels of these cell lines.