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The role of hydroxyl radical as a messenger in Cr(VI)-induced p53 activation.

Authors
Wang-S; Leonard-SS; Ye-J; Ding-M; Shi-X
Source
Am J Physiol, Cell Physiol 2000 Sep; 279(3):C868-C875
NIOSHTIC No.
20020846
Abstract
The present study investigates whether reactive oxygen species (ROS) are involved in p53 activation, and if they are, which species is responsible for the activation. Our hypothesis is that hydroxyl radical (OH) functions as a messenger for the activation of this tumor suppressor protein. Human lung epithelial cells (A549) were used to test this hypothesis. Cr(VI) was employed as the source of ROS due to its ability to generate a whole spectrum of ROS inside the cell. Cr(VI) is able to activate p53 by increasing the protein levels and enhancing both the DNA binding activity and transactivation ability of the protein. Increased cellular levels of superoxide radicals (O(2)(-).), hydrogen peroxide (H(2)O(2)), and OH radicals were detected on the addition of Cr(VI) to the cells. Superoxide dismutase, by enhancing the production of H(2)O(2) from O(2)(-) radicals, increased p53 activity. Catalase, an H(2)O(2) scavenger, eliminated OH radical generation and inhibited p53 activation. Sodium formate and aspirin, OH radical scavengers, also suppressed p53 activation. Deferoxamine, a metal chelator, inhibited p53 activation by chelating Cr(V) to make it incapable of generating radicals from H(2)O(2) NADPH, which accelerated the one-electron reduction of Cr(VI) to Cr(V) and increased OH radical generation, dramatically enhanced p53 activation. Thus OH radical generated from Cr(VI) reduction in A549 cells is responsible for Cr(VI)-induced p53 activation.
Keywords
Tumors; Proteins; Lung-cells; Peroxides; Chelates; Chelating-agents; Sodium-compounds; Carcinogenesis; Carcinogenicity; Carcinogens; Antioxidants; Antioxidation
CAS No.
7722-84-1; 7440-23-5
Publication Date
20000901
Document Type
Journal Article
Email Address
xas0@cdc.gov
Fiscal Year
2000
NTIS Accession No.
NTIS Price
Issue of Publication
3
ISSN
0363-6143
NIOSH Division
HELD
Source Name
American Journal of Physiology: Cell Physiology
State
WV
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