DNA damage-inducible genes as biomarkers for exposures to environmental agents
- Inhalation Toxicology Research Institute, Albuquerque, NM (United States)
A biodosimetric approach to determine alpha-particle dose to the respiratory tract epithelium from known exposures to radon has been developed in the rat. Cytotoxicity assays have been used to obtain dose-conversion factors for cumulative exposures typical of those encountered by underground uranium miners. However, this approach is not sensitive enough to derive close-conversion factors for indoor radon exposures. The expression of DNA damage-inducible genes is being investigated as a biomarker of exposure to radon progeny. Exposure of cultures of A549 cells to alpha particles resulted in an increase in the protein levels of the DNA damage-inducible genes, p53, Cip 1, and Gadd45. These protein changes were associated with a transient arrest of cells passing through the cell cycle. This arrest was typified by an increase in the number of cells in the G{sub 1} and G{sub 2} phases and a decrease in the number of cells in the S phase. The effect of inhaled alpha particles (radon progeny) in rats was examined in the epithelial cells of the lateral wall of the anterior nasal cavity. Exposures to radon progeny resulted in a significant increase in the number of cells in the G{sub 1} phase and a decrease in the number of cells in the S phase. These cell-cycle changes were concomitant with an increase in the number of cells containing DNA strand breaks. In addition to ionizing radiation, A549 cells were exposed to 4-nitroquinoline-1-oxide, methyl methanesulphonate, crocidolite asbestos, and glass microfiber. These studies showed that physical and chemical agents induce different expression patterns of p53, Cip 1, and Gadd153 proteins and they could be used to discriminate between toxic and nontoxic materials such as asbestos and glass microfiber. The measurement of gene expression in A549 cells may provide a means to identify a broad spectrum of physical and chemical toxicants encountered in the environment. 9 figs., 42 refs.
- Sponsoring Organization:
- USDOE
- DOE Contract Number:
- AC04-76EV01013
- OSTI ID:
- 588652
- Journal Information:
- Environmental Health Perspectives, Vol. 105, Issue Suppl.4; Other Information: PBD: Jun 1997
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BASIC STUDIES
56 BIOLOGY AND MEDICINE
APPLIED STUDIES
54 ENVIRONMENTAL SCIENCES
ALPHA PARTICLES
SENSITIVITY
GENE REGULATION
ANIMAL CELLS
INHALATION
TOXICITY
IONIZING RADIATIONS
ASBESTOS
CELL CYCLE
DNA
EPITHELIUM
GENES
PROGENY
PROTEINS
RADON
RATS
STRAND BREAKS
GENETIC EFFECTS
GENETIC RADIATION EFFECTS
GENE MUTATIONS
BIOLOGICAL MARKERS
ENVIRONMENTAL EXPOSURE
RADIATION DOSE DISTRIBUTIONS
DOSE-RESPONSE RELATIONSHIPS
RADIATION DOSES
RESPIRATORY SYSTEM
CUMULATIVE RADIATION EFFECTS
OCCUPATIONAL EXPOSURE
URANIUM MINES
METHYL METHANESULFONATE