Involvement of ATM/ATR-p38 MAPK cascade in MNNG induced G1-S arrest.
World J Gastroenterol
; 9(9): 2073-7, 2003 Sep.
Article
en En
| MEDLINE
| ID: mdl-12970909
ABSTRACT
AIM:
To understand the effect of low concentration of N-methyl-N'-nitro-nitrosoguanidine (MNNG), which is a widely distributed environmental mutagen and carcinogen especially for human gastric cancer, on DNA damage and to study its possible pathway in regulating cell cycle arrest.METHODS:
The DNA damage effect was measured by Comet assay. A specific phospho-(Ser/Thr) ATM/ATR substrate antibody was used to detect the damage sensor by Western blot. p38 kinase activity was measured by direct kinase assay, and immunoprecipitation for the possible connection between ATM/ATR and p38 MAPK. Flow cytometry analysis and p38 MAPK specific inhibitor SB203580 were combined to detect the possible cell cycle arrest by p38 MAPK.RESULTS:
With the same low concentration MNNG exposure (0.2 microM 2.5 h), Comet assays indicated that strand breaks accumulated, Western blot and kinase assay showed ATM/ATR and p38 kinase activated, immunoprecipitation showed phospho-ATM/ATR substrate antibody combined with both p38 MAPK antibody and phospho-p38 MAPK antibody. p38 MAPK pathway was involved in the G1-S arrest.CONCLUSION:
Activation of ATM/ATR by MNNG induced DNA damage leads to activation of p38 MAPK, which involves in the G1 checkpoint in mammalian cells.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Fase G1
/
Fase S
/
Proteínas Serina-Treonina Quinasas
/
Proteínas de Ciclo Celular
/
Proteínas Quinasas Activadas por Mitógenos
/
Metilnitronitrosoguanidina
Límite:
Animals
Idioma:
En
Revista:
World J Gastroenterol
Asunto de la revista:
GASTROENTEROLOGIA
Año:
2003
Tipo del documento:
Article
País de afiliación:
China