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The Involvement of p53 in Paraquat-Induced Apoptosis in Human Lung Epithelial-Like CellsDepartment of Emergency and Critical Care Medicine, Kansai Medical University, Osaka, Japan Correspondence: Address correspondence to Naoshi Takeyama, Department of Emergency and Critical Care Medicine, Kansai Medical University, Fumizono-cho 10–15, Moriguchi, Osaka, 570–8507, Japan. E-mail:takeyama{at}takii.kmu.ac.jp 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.
Key Words: Apoptosis • L132 • Paraquat • p53 • U937
International Journal of Toxicology, Vol. 23, No. 1,
33-40 (2004) |
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