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

Abstract

Previous studies of the expression of SV40 genetic information by skin fibroblasts included limited numbers of cell donors and failed to adequately consider possible effects of age, sex, and ethnic origin on assay results. A population of 76 healthy subjects were selected for study following determination of personal and family disease history and karyological analysis. Skin fibroblasts from these individuals were tested for expression of SV40 T-antigen by indirect immunofluorescent assay. The data were normally distributed and showed no significant differences between the age, sex, or ethnic groups tested. The occurrence of rare karyological anomalies in this control population had no effect on T-antigen expression. Fibroblasts from 10 Fanconi anemia patients demonstrated significantly elevated expression of T antigen compared to the well-defined control population, based on simple statistical criteria. T-antigen expression was elevated in two young patients prior to the onset of anemia and did not appear to correlate with the incidence or severity of other specific symptoms. Thus, elevated T-antigen expression in Fanconi anemia fibroblasts reflects an actual defect at the cellular level, rather than clinical, age, sex or ethnic factors not previously considered.

Relationship of SV40 T‐antigen expression in vitro to disorders of bone marrow function

“…Clinical findings are summarized in Table I. Since the initial report [3] normalities in leukocytes and fibroblasts without evidence of congenital anomalies were The origin, propagation, and titration of the small plaque isolate of SV40 employed SV40-T-antigen was measured by an indirect immunofluorescent assay [13] . ReTwo families had multiple cases of aplastic anemia occurring later in life, which is Seven cases of sporadic (nonfamilial) aplastic anemia were studied.…”

“…In each encoded culture, 100 microscopic fields (approximately 3,000 cells) were examined for the presence or absence of SV40 T-antigen. A mean proportion (pw) was calculated for each cell line, weighed according to the number of cells examined per replicate, and methematically transformed by the arc sin square root function (sin-' J p w ) to allow parametric statistical comparison to a normal population of 76 healthy controls [3] . The sin-' J p w value for a given cell line was compared to the control population by the cumulative normal probability function (z-test).…”

“…Clinical findings are summarized in Table I. Since the initial report [3] , FA case 1802 remains free of hematologic abnormalities at age seven. FA case 2356, with normal marrow function at age 12 months [3] , developed thrombocytopenia at 18 months and pancytopenia at 30 months [ 141 .…”

“…Since the initial report [3] , FA case 1802 remains free of hematologic abnormalities at age seven. FA case 2356, with normal marrow function at age 12 months [3] , developed thrombocytopenia at 18 months and pancytopenia at 30 months [ 141 . Cases 2628 and 2629 are sisters wtih typical clinical stigmata of FA, except that case 2629 has not shown hematologic symptoms at age seven.…”

“…Four-digit numbers refer to cell line codes. The data for eight cases of Fanconi anemia (shown without cell line codes) have been previously reported by us[ 3 ] . The small dot and bar in panel A refer to the group mean f standard error.…”