PMID- 1357059 OWN - NLM STAT- MEDLINE DCOM- 19921029 LR - 20190907 IS - 0955-3002 (Print) IS - 0955-3002 (Linking) VI - 62 IP - 4 DP - 1992 Oct TI - Transformation and radiosensitivity of human diploid skin fibroblasts transfected with SV40 T-antigen mutants defective in RB and P53 binding domains. PG - 461-8 AB - A series of human diploid fibroblast cell clones were developed by DNA transfection with either wild-type SV40 T-antigen (SV40 T) or T-antigen mutants defective in its various functional domains. Cell clones expressing the wild-type SV40 T were significantly radioresistant as compared with clones transfected with the neo gene only (D0 = 192 +/- 13 vs 127 +/- 19). This radioresistance persisted in post-crisis, immortalized cell lines. A series of mutants with point or deletion mutations within each functionally active domain of SV40 T were also examined for their ability to alter radiosensitivity and induce morphological transformation. Cell clones transfected with T-antigen mutants defective in nuclear localization or origin binding showed increased radioresistance similar to clones transfected with wild-type T-antigen, and expressed morphological changes characteristic of SV40 T-transfected cells. A retinoblastoma susceptibility gene (RB) binding defective mutant showed moderately increased radioresistance (D0 = 174 +/- 10). However, cell clones transfected with three different p53 binding defective mutants showed no change in radiosensitivity (D0 = 132 +/- 5) as compared with neo gene transfected controls. Transfection with T-antigen mutants defective in either the RB or p53 binding domain yielded no morphological alterations characteristic of transformation. These data suggest that the SV40 T/p53 complex may be of importance in the radioresistance phenotype. FAU - Su, L N AU - Su LN AD - Laboratory of Radiobiology, Harvard School of Public Health, Boston, Massachusetts 02115. FAU - Little, J B AU - Little JB LA - eng GR - CA-47542/CA/NCI NIH HHS/United States GR - ES-00002/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Int J Radiat Biol JT - International journal of radiation biology JID - 8809243 RN - 0 (Antigens, Polyomavirus Transforming) SB - IM GS - RB GS - p53 MH - Antigens, Polyomavirus Transforming/chemistry/*genetics MH - Cell Adhesion MH - Cell Line MH - Cell Survival MH - Cell Transformation, Viral/*genetics/radiation effects MH - Colony-Forming Units Assay MH - Diploidy MH - Fibroblasts MH - *Genes, Retinoblastoma MH - *Genes, p53 MH - Humans MH - Infant, Newborn MH - Male MH - Mutation MH - *Radiation Tolerance MH - Skin/cytology MH - *Transfection EDAT- 1992/10/01 00:00 MHDA- 1992/10/01 00:01 CRDT- 1992/10/01 00:00 PHST- 1992/10/01 00:00 [pubmed] PHST- 1992/10/01 00:01 [medline] PHST- 1992/10/01 00:00 [entrez] AID - N5BWX68C2C26QHP4 [pii] AID - 10.1080/09553009214552341 [doi] PST - ppublish SO - Int J Radiat Biol. 1992 Oct;62(4):461-8. doi: 10.1080/09553009214552341.