We have developed a system of ultraviolet-light induced transformation of human cells to anchorage-independent growth; we shall study the influence of age and origin of the effects of cell cycle and irradiation schedule, as well as the role of DNA repair and/or misrepair on the transformation frequency. We shall characterize the growth properties, karyotype and tumorigenicity of the transformants. We have developed an alkaline agarose gel electrophoresis method of measuring low levels of pyrimidine dimers in non-radioactive DNA of human skin or cultured cells. We shall measure the action spectrum for pyrimidine dimer formation in human skin. We shall determine whether sunscreening agents and sunlamp radiation sensitize pyrimidine dimer production in human skin. We shall use the gel electrophoresis method to measure DNA repair in human cells and skin; we shall determine the relative roles of excision repair and photoreversal in human skin. We shall measure the action spectrum for dimer reversal to determine if it is mediated by the photoreactivating enzyme. We shall determine the relationship of DNA damage and repair to solar oncogenesis; we shall measure DNA repair in biopsies of normal and of sunsensitive, skin-cancer prone individuals. We shall establish cultures from biopsies of these individuals and shall determine UV transformation frequencies and DNA repair capacities of these cells. We shall assess the ability of in vitro DNA repair measurements to describe accurately in vivo repair rates in man. We shall determine the relationship between in vitro UV-transformation frequencies and propensity to sunlight-induced skin cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA026492-08
Application #
3167336
Study Section
Radiation Study Section (RAD)
Project Start
1979-07-01
Project End
1987-12-31
Budget Start
1987-01-01
Budget End
1987-12-31
Support Year
8
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Associated University-Brookhaven National Lab
Department
Type
DUNS #
City
Upton
State
NY
Country
United States
Zip Code
11973
Sutherland, B M; Freeman, A G; Bennett, P V (1988) Human cell transformation in the study of sunlight-induced cancers in the skin of man. Mutat Res 199:425-36
Freeman, S E; Gange, R W; Sutherland, J C et al. (1987) Production of pyrimidine dimers in DNA of human skin exposed in situ to UVA radiation. J Invest Dermatol 88:430-3
Spadari, S; Sutherland, B M; Pedrali-Noy, G et al. (1987) Alteration of DNA tertiary structure by physical and chemical carcinogens: involvement in DNA repair processes. Toxicol Pathol 15:82-7
Freeman, S E; Gange, R W; Sutherland, J C et al. (1987) Pyrimidine dimer formation in human skin. Photochem Photobiol 46:207-12
Sutherland, B M; Ciarrocchi, G; Ciomei, M et al. (1986) Quantitation of DNA damage in non-radioactive DNA. Photochem Photobiol 44:391-6
Freeman, S E; Gange, R W; Matzinger, E A et al. (1986) Higher pyrimidine dimer yields in skin of normal humans with higher UVB sensitivity. J Invest Dermatol 86:34-6
Freeman, S E; Blackett, A D; Monteleone, D C et al. (1986) Quantitation of radiation-, chemical-, or enzyme-induced single strand breaks in nonradioactive DNA by alkaline gel electrophoresis: application to pyrimidine dimers. Anal Biochem 158:119-29
Sutherland, B M; Blackett, A D; Feng, N I et al. (1985) Photoreactivation and other ultraviolet/visible light effects on DNA in human skin. Ann N Y Acad Sci 453:73-9
Ciarrocchi, G; Sutherland, B M; Sutherland, J C (1985) Incandescent lamps can produce pyrimidine dimers in DNA. Photochem Photobiol 41:703-5
Sutherland, B M; Bennett, P V; Freeman, A G et al. (1985) Transformation of human cells by DNAs ineffective in transformation of NIH 3T3 cells. Proc Natl Acad Sci U S A 82:2399-403

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