Skin Fibroblasts from Humans Genetically Predisposed to Colon Cancer are Abnormally Sensitive to SV40

Abstract

Experimental conditions that best distinguish the abnormal susceptibility to SV40 found in skin fibroblasts from patients with hereditary adenomatosis of the colon and rectum (ACR) are reported. T-Antigen expression of these SV40-in-fected human cells was largely dependent on cell density and was optimal at a concentration of 1000-2000 cells/cm². Significantly, the abnormal susceptibility of ACR cells to SV40 was greatest and most reproducible at this density. The transformation of these cells by SV40 was also dependent on the multiplicity of infection (MOI), represented by the linear portion of the curve (range about 100-1000 pfu) for both normal and ACR cells. Under these conditions, ACR cells were about sixfold more sensitive to SV40-induced T-antigen expression and transformation. These results provide additional support for the use of SV40 to identify humans at risk from ACR families as well as other dominantly transmitted forms of human cancer.