CR (VI) induces cell growth arrest through hydrogen peroxide-mediated reactions

Citation
Z. Zhang et al., CR (VI) induces cell growth arrest through hydrogen peroxide-mediated reactions, MOL C BIOCH, 222(1-2), 2001, pp. 77-83
Citations number
38
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
MOLECULAR AND CELLULAR BIOCHEMISTRY
ISSN journal
0300-8177 → ACNP
Volume
222
Issue
1-2
Year of publication
2001
Pages
77 - 83
Database
ISI
SICI code
0300-8177(200106)222:1-2<77:C(ICGA>2.0.ZU;2-2
Abstract
Cr (VI) compounds are widely used in industries and are recognized human ca rcinogens. The mechanism of carcinogenesis associated with these compounds is not well understood. The present study focused on Cr (VI)-induced cell g rowth arrest in human lung epithelial A549 cells, using flow cytometric ana lysis of DNA content. Treatment of the cells with Cr (VI) at 1 muM caused a growth arrest at G(2)/M phase. An increase in Cr (VI) concentration enhanc ed the growth arrest. At a concentration of 25 muM, Cr (VI)-induced apoptos is became apparent. Superoxide dismutase (SOD) or sodium formate did not al ter the Cr (VI)-induced cell growth arrest. While catalase inhibited growth , indicating H2O2 is an important mediator in Cr (VI)-induced G(2)/M phase arrest. Electron spin resonance (ESR) spin trapping measurements showed tha t incubation of cells with Cr (VI) generated hydroxyl radical ((OH)-O-.). C atalase inhibited the (OH)-O-. radical generation, indicating that H2O2 was generated from cells stimulated by Cr (VI), and that H2O2 functioned as a precursor for (OH)-O-. radical generation. The formation of H2O2 from Cr (V I)-stimulated cells was also measured by the change in fluorescence of scop oletin in the presence of horseradish peroxidase. The mechanism of reactive oxygen species generation involved the reduction of molecular oxygen as sh own by oxygen consumption assay. These results support the following conclu sions: (a) Reactive oxygen species are generated in Cr (VI)-stimulated A549 cells through reduction of molecular oxygen, (b) Among the reactive oxygen species generated, H2O2 played a major role in causing G(2)/M phase arrest in human lung epithelial cells.