Projects and Grants per year
Grants and Contracts Details
Description
Arsenic (As) is a well-documented human carcinogen. Environmental and occupational exposures to
As-containing compounds are major public health issues. Understanding the mechanism of As-induced
carcinogenesis is very important for early detection, for risk assessment, for establishment of an exposure
standard, and for development of intervention and prevention strategies. While increasing evidence has linked
arsenic exposure and generation of reactive oxygen species (ROS), we do not clearly understand the exact
nature of the specific reactive species, the source and mechanism of ROS generation, the sequence of
formation of different reactive species, and the specific species that are responsible for the arsenic-induced
carcinogenesis. The goal of this proposal is to test the hypothesis that As-induced carcinogenesis is mediated
by oxidative stress. To test this hypothesis, we will: (a) identify the molecular mechanism of As-induced ROS
generation in cells with emphisis on 02·- radical generation since this radical is a precursor of other reactive
oxygen species; (b) determine oxidative stress, lipid peroxidation, protein oxidation, and oxidative DNA
damage following As exposure in vivo; and (c) elucidate the role of oxidative stress in As-induced cell
transformation and tumorigenesis. We will use As-treated HaCat cells to examine As-induc~d tumorigenesis in
athymic nude mice and investigate the involvement of specific ROS species. We anticipate that As generates
ROS, which cause activation of NF-DB and activator protein (AP-1) leading to tumorigenesis in nude mice.
The results obtained from this proposal will provide a fundamental understanding concerning the role of ROS
in As-induced carcinogenesis.
Status | Finished |
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Effective start/end date | 2/1/06 → 12/31/10 |
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Projects
- 1 Finished