Solar ultraviolet (UV) radiation is a proven mutagen, toxicant, and carcinogen; little is known, however, about the underlying chemical processes causing these effects. We have recently established that reactive species of oxygen are generated by solar UV from endogenously occurring cellular photosensitizers in photodynamic-type reactions and are important intermediates in the biological effects of these radiations, especially at wavelengths longer than about 320 nm. The identities of these species and the mechanisms through which they exert biological effects are not known. We propose to combine the chemical expertise in reactive oxygen species chemistry, biochemistry, and methodology of C.S. Foote and N. I. Krinsky with the photobiological expertise of M. J. and J. G. Peak to elucidate the nature and mechanisms of action of the specific reactive oxygen species generated. These experiments, using mutagenesis in E. coli and damage in isolated bacterial DNA as end points, will provide insights into the basic molecular mechanisms whereby these reactive intermediates exert their biological effects. These insights may provide information relevant to our understanding of a possible role of the reactive oxygen species in carcinogenesis, since solar UV radiations are the main etiological factor in the induction of more than 70% of all human cancers. This information will also improve our understanding of hazards caused by the possible enhanced fluxes of solar UV radiation reaching the earch as a consequence of the attenuation of our stratospheric ozone shield.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA037848-02
Application #
3175706
Study Section
Radiation Study Section (RAD)
Project Start
1984-08-15
Project End
1987-07-30
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
Peak, J G; Peak, M J (1995) Induction of slowly developing alkali-labile sites in human P3 cell DNA by UVA and blue- and green-light photons: action spectrum. Photochem Photobiol 61:484-7
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; 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
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

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