Heterotransplantation studies with tissue culture cell lines in various animal and in vitro host systems.

The human amnion cell line FL was found to be more tumorigenic than HeLa cells when used as a positive control in heterotransplantation assays. FL cells formed significantly larger locally invasive tumors than HeLa cells in both Balb/c/nu/nu mice and ATG-treated newborn Wistar rats. In addition, FL cells resulted in metastatic growths in the lungs of two of 12 mice six weeks and in 10 of 36 rats three weeks after inoculation. HeLa cells did not produce metastases in either mice or rats. Both these cell lines were obtained from the American Type Culture Collection. Heterotransplantation experiments with a variety of animal host systems confirmed previous findings that newborn Wistar rats treated with rat ATG were the most sensitive to tumor growth. Vero and LLC-MK2 continuous monkey kidney cells formed small, non-progressively growing tumors showing tubule formation and occasional mitoses. LLC-MK2 cells were found to be more pleomorphic in appearance and with more mitoses than Vero cells but neither cell line showed any evidence of distant metastatic growth in any of several organs examined. The human lymphoblastoid cell line Namalwa produced large invasive tumors at the inoculation site but no distant metastases. In the chick embryo skin test it was found that MI values (mitotic index--percentage of cells in mitosis) gave more reproducible results and were less time-consuming than counting mean mitoses per section. Significant differences were found between Vero, LLC-MK2, HeLa and FL cells with Vero giving the lowest and FL the highest values. The use of MI values enhanced the sensitivity of the chick embryo skin test which was found to be a rapid and valuable screening test for tumorigenicity.