Radiation-induced mutations at the autosomal thymidine kinase locus are not elevated in p53-null cells.
To explore further the possibility that some forms of mutated p53 may increase mutagenesis in a positive manner, a double p53 knockout cell line was created, using a promoterless gene targeting approach. The identity of these p53-null cells was confirmed by Southern blot and Western blot analyses. Radiation-induced toxicity and mutagenicity was then compared among p53-null cells, TK6 cells with wild-type p53, and WTK1 cells with a p53 point mutation in codon 237. At the autosomal, heterozygous thymidine kinase locus, p53-null cells had equivalent background mutation frequencies and were approximately equally mutable as TK6, whereas WTK1 was much more sensitive to spontaneously arising and X-ray-induced mutation. Thus, these results indicate that the lack of wild-type p53 did not lead to increased mutagenesis.
Chuang
Y Y
YY
Department of Radiation Oncology, Massachusetts General Hospital, Boston 02114, USA.
Chen
Q
Q
Brown
J P
JP
Sedivy
J M
JM
Liber
H L
HL
D002460:Cell Line; D004307:Dose-Response Relationship, Radiation; D005796:Genes / Q000528:radiation effects*; D016158:Genes, p53; D006801:Humans; D008214:Lymphocytes; D016296:Mutagenesis; D017354:Point Mutation; D013937:Thymidine Kinase / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics*; D014965:X-Rays
D016159:Tumor Suppressor Protein p53; D013937:Thymidine Kinase