The involvement of p53 in paraquat-induced apoptosis in human lung epithelial-like cells.
To investigate the possible role of p53 in the progression of paraquat-induced apoptosis, the authors used two cell lines that were wild-type p53-expressing human lung epithelial-like cell line (L132) and a p53-deficient human promyelocytic leukemia cell line (U937) and explored the linkage between p53, DNA damage, and apoptosis. Following paraquat exposure to L132 cells, the percentage of S-phase cells decreased significantly and the expression of p53 protein increased, suggesting that entry into S phase from G1 phase was blocked. U937 cells showed complete resistance to paraquat, although paraquat-evoked initial single-stranded DNA breaks was shown equally in either L132 or U937 cells, as assessed by single-cell gel electrophoresis. U937 and L132 cells die normally with similar kinetics when exposed to tumor necrosis factor in the presence of cycloheximide, indicating that their capacity to undergo p53-independent mechanisms of inducing apoptosis has an equal rate. These results suggest that paraquat-induced DNA damage caused G1 arrest and apoptosis only in L132 cells, and that p53 protein accumulation is required for the induction of apoptosis by paraquat.
Takeyama
Naoshi
N
Department of Emergency and Critical Care Medicine, Kansai Medical University, Osaka, Japan. takeyama@takii.kmu.ac.jp
Tanaka
Takaya
T
Yabuki
Teru
T
Nakatani
Toshio
T
D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects*; D004996:Ethidium; D005456:Fluorescent Dyes; D016158:Genes, p53 / Q000235:genetics*; D006540:Herbicides / Q000633:toxicity*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008168:Lung / Q000166:cytology* / Q000187:drug effects; D018613:Microscopy, Confocal; D010269:Paraquat / Q000633:toxicity*; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D005456:Fluorescent Dyes; D006540:Herbicides; D016159:Tumor Suppressor Protein p53; D004996:Ethidium; D010269:Paraquat