Hypermutable Change of Human UVr-1 Cells by p53 Overexpression

Autor: Sugita, Tatsuya, Hiwasa, Takaki, Nomura, Jun, Kita, Kazuko, Hiroshima, Kenzo, Suzuki, Hideko, Sekiya, Soei, Suzuki, Nobuo
Zdroj: Biochemical and Biophysical Research Communications; December 7, 2001, Vol. 289 Issue: 3 p756-762, 7p
Abstrakt: 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 UVr-1 cells, a hypomutable variant of RSa cells, showed a delayed increase. Three cell lines overexpressing wild-type p53 in UVr-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.
Databáze: Supplemental Index