Although solar ultraviolet radiation is a proven mutagen, toxicant, and carcinogen, little is known about the underlying cellular and molecular processes causing these effects in mammalian cells, especially by the longer ultraviolet wavelengths. Using human cells (P3 teratocarcinoma) in culture and an isolated fragment of human DNA, we propose (1) to study the spectral efficiencies for specific DNA alterations (breakage, protein cross-links, pyrimidine dimers, and (6-4) pyrimidine adducts) caused by wavelengths longer than 290 nm, and (2) to attempt to correlate the specific DNA lesions observed with mutagenesis and cell killing caused by solar uv. Isolated wavelength bands and lines within the 290 to 435 nm range as well as the complete spectrum of terrestrial solar radiation itself (290 through visible light) will be used. The effects of dose modifying reagents, especially oxygen, upon the biological and biophysical end points will be studied. These experiments will provide insight into basic molecular mechanisms of the biological action of solar ultraviolet light, and provide information relevant to our understanding of hazards resulting from possible attenuation of our stratospheric ozone shield.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA034492-02
Application #
3172217
Study Section
Radiation Study Section (RAD)
Project Start
1984-08-01
Project End
1987-07-31
Budget Start
1985-08-01
Budget End
1986-07-31
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Chicago
Department
Type
Organized Research Units
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637
Chen, W; Blazek, E R; Rosenberg, I (1995) The relaxation of supercoiled DNA molecules as a biophysical dosimeter for ionizing radiations: a feasibility study. Med Phys 22:1369-75
Blazek, E R; Alderfer, J L; Tabaczynski, W A et al. (1993) A 5-4 pyrimidine-pyrimidone photoproduct produced from mixtures of thymine and 4-thiouridine irradiated with 334 nm light. Photochem Photobiol 57:255-65
Dudek, E J; Peak, J G; Roth, R M et al. (1993) Isolation of V79 fibroblast cell lines containing elevated metallothionein levels that have increased resistance to the cytotoxic effects of ultraviolet-A radiation. Photochem Photobiol 58:836-40
Blazek, E R; Peak, J G (1992) Filter elution assays for DNA damage: practical and mechanistic significance of the DNA in the filter support wash. Radiat Res 130:384-8
Churchill, M E; Peak, J G; Peak, M J (1991) Repair of near-visible- and blue-light-induced DNA single-strand breaks by the CHO cell lines AA8 and EM9. Photochem Photobiol 54:639-44
Peak, J G; Pilas, B; Dudek, E J et al. (1991) DNA breaks caused by monochromatic 365 nm ultraviolet-A radiation or hydrogen peroxide and their repair in human epithelioid and xeroderma pigmentosum cells. Photochem Photobiol 54:197-203
Churchill, M E; Peak, J G; Peak, M J (1991) Correlation between cell survival and DNA single-strand break repair proficiency in the Chinese hamster ovary cell lines AA8 and EM9 irradiated with 365-nm ultraviolet-A radiation. Photochem Photobiol 53:229-36
Peak, J G; Peak, M J (1991) Comparison of initial yields of DNA-to-protein crosslinks and single-strand breaks induced in cultured human cells by far- and near-ultraviolet light, blue light and X-rays. Mutat Res 246:187-91
Peak, M J; Peak, J G (1990) Hydroxyl radical quenching agents protect against DNA breakage caused by both 365-nm UVA and by gamma radiation. Photochem Photobiol 51:649-52
Peak, J G; Peak, M J (1990) Ultraviolet light induces double-strand breaks in DNA of cultured human P3 cells as measured by neutral filter elution. Photochem Photobiol 52:387-93

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