Hypermutable change of human UV(r)-1 cells by p53 overexpression.
The p53 protein has been reported to regulate cellular responses to genetic stress such as far-ultraviolet light (UV), protecting human cells from mutation. Levels of p53 protein in hypermutable RSa cells were found here to increase soon after UV irradiation, while those in UV(r)-1 cells, a hypomutable variant of RSa cells, showed a delayed increase. Three cell lines overexpressing wild-type p53 in UV(r)-1 cells exhibited higher sensitivity to UV mutagenicity than did control U-V-7 cells transfected with vector alone, assessed using the ouabain-resistance phenotypic mutation test and identification of K-ras codon 12 base substitution mutation. On the other hand, U-V-7 cells showed UV-induced elevation of antipain-sensitive protease activity, but p53 transfectants did not. Moreover, antipain treatment to U-V-7 cells was increased susceptibility to UV mutagenicity. Thus, p53 protein overproduction may sensitize human cells, at least those tested, to UV mutagenicity, in association with inhibition of protease activity.
Sugita
T
T
Department of Reproductive Medicine, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chiba-shi, Chuo-ku, Chiba, 260-8670, Japan.
Hiwasa
T
T
Nomura
J
J
Kita
K
K
Hiroshima
K
K
Suzuki
H
H
Sekiya
S
S
Suzuki
N
N
D002455:Cell Division / Q000528:radiation effects; D002460:Cell Line; D002999:Clone Cells; D004307:Dose-Response Relationship, Radiation; D010450:Endopeptidases / Q000378:metabolism; D011905:Genes, ras / Q000528:radiation effects; D006801:Humans; D007700:Kinetics; D016296:Mutagenesis; D009152:Mutagenicity Tests; D011836:Radiation Tolerance; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays
D016159:Tumor Suppressor Protein p53; D010450:Endopeptidases