Abnormal response to DNA crosslinking agents of XXXX fibroblasts can be corrected by transfection with normal @entity1 DNA.

@entity1 @entity1138 @entity9627 @entity1139 @entity375 @entity11807
Primary skin fibroblast cell lines from @entity1 with @entity11807 were cotransfected with UV-irradiated pSV2neo plasmids and high molecular weight DNA from normal @entity1 cells. Restoration of a normal cellular resistance to @entity1138 ( @entity1139 ) was observed provided that a @entity11807 cell line is selected for DNA-mediated transformation (neo gene) and that at least two successive rounds of transfection are performed. Cells were selected by taking advantage of the higher proliferation rate and plating efficiency of the @entity1139 resistant transformants. As estimated from reconstruction experiments, the frequency of transfer of @entity1139 resistance lies between 1 and 30 X 10(-7). The @entity1139 resistance phenotype was maintained for at least 10 generations following transfection. Evidence for DNA-mediated transformation also includes the recovery of a normal pattern of DNA semiconservative synthesis after treatment with @entity9627 and 365-nm UV irradiation, and the presence of exogenous pSV2neo DNA sequences was shown by Southern blot analysis. The acquired @entity1139 resistance is probably due to the presence of DNA from normal cells. Indeed, sensitivity to @entity1139 was maintained when @entity11807 cells were cotransfected with the UV-irradiated pSV2neo plasmid mixed with their own DNA or with @entity375 or salmon sperm DNA. These negative results also render unlikely the selection of spontaneous @entity1139 resistant revertants in transfection of @entity11807 cells with normal DNA. These experiments establish the prerequisites for the isolation of the gene(s) involved in the response to DNA crosslinking lesions in @entity1 cells.
