Transformation of human cells by SV40 virus

Abstract

Fibroblast cultures were prepared from skin biopsies from 29 patients and tested for their susceptibility to transformation by simian virus SV40. Cells with a normal chromosome complement showed a mean transformation frequency of 25/106 cells but for cells from a single patient with Fanconi's anaemia, the value was 152/106 cells. An increased susceptibility to transformation was observed for cells from 6 patients with Down's syndrome 3 patients with trisomy 18, a patient with trisomy 18 for 5% of cells and a patient with trisomy 13. No increased susceptibility to transformation was found for cells with a chromosome complement of XO, XXY, XX/XX + 8, XX + partial 15q or XX + 9p. The susceptiability to transformation was related to susceptibility to SV40 virus infection, as measured by the number of infected cells which contained SV40 virus induced T antigen. This latter test was technically easier to perform and could serve to detect persons of increased susceptiability to transformation, since this may indicate an increased risk of natural malignant disease.

Sv40 t‐antigen expression in skin fibroblasts from clinically normal individuals and from ten cases of fanconi anemia

“…Todaro and co-workers (1) reported that skin fibroblasts derived from Fanconi anemia patients exhibited a higher incidence of colony or focus formation (transformation) than cells from normal individuals following infection with simian virus 40 (SV40) in vitro. This finding has been confirmed in other laboratories (2)(3)(4)(5). It was postulated that SV40 transformation may represent an in vitro marker for high cancer risk in genetic disorders such as Fanconi anemia and Down's syndrome (6).…”

“…It was postulated that SV40 transformation may represent an in vitro marker for high cancer risk in genetic disorders such as Fanconi anemia and Down's syndrome (6). SV40-infected cells from Fanconi anemia patients also express SV40 T-antigen more frequently than cells from normal individuals (3,7). Since the incidence of SV40 T-antigen is correlated with the incidence of colony formation (3, 7, S), the relatively short-term immunofluorescent T-antigen assay (requiring 3 days of incubation) may be more easily applied to large populations than the tedious transformation assay requiring 21 days of incubation (7,8).…”

Chromosome complement and SV40 transformation of cells from patients susceptible to malignant disease

“…The presence of other balanced translocations in A-T or A-T heterozygote cells did not cause raised transformation rates, so the presence of a clone per se does not appear to predispose the cell line to transformation, although it is possible to envisage that specific translocations may exert an effect. Potter and Potter (1975) found certain trisomic cells to be susceptible to SV40 transformation while others were not.…”

Genetics and Disease

“…There are some suggestions that cells from these groups of patients are more susceptible to transformation by SV40 virus (e.g. Potter & Potter 1975). However, the low level of this increased susceptibility and the variability of this test leaves room for doubt that this is necessarily a demonstration of the underlying mechanism of susceptibility.…”