This research focuses on the molecular and biochemical origins of sunlight-induced skin cancers in man. It addresses three aspects of the problem: (1) sunlight-induced damage to DNA, (2) cellular enzymes for repair of such damage and (3) consequences of failure of repair. These problems are studied in four experimental approaches: first, delineation of the kinds, number and distribution of DNA lesions induced in human skin irradiated in situ, in neonatal human foreskins and in isolated DNA by irradiation with radiation in the wavelength range of 220-400 nm; second, determination of the paths and rates of repair of such DNA lesions in skin irradiated in situ; third, study of the activity and structure of DNA repair enzymes, in specific, DNA photoreactivating enzymes from man and E. coli; and fourth, determination of the molecular changes in DNA of sunlight-induced skin cancers using a human cell DNA transfection system developed in this laboratory. These studies should give insights into solar oncogenesis in man, from introduction of the initial lesion, cellular repair and/or failure of repair, and molecular changes in DNA in human skin cancers.

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National Cancer Institute (NCI)
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Radiation Study Section (RAD)
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Associated University-Brookhaven National Lab
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Sutherland, B M; Bennett, P V; Sutherland, J C (1999) DNA damage quantitation by alkaline gel electrophoresis. Methods Mol Biol 113:183-202
Bennett, P V; Gange, R W; Hacham, H et al. (1996) Isolation of high-molecular-length DNA from human skin. Biotechniques 21:458-63
Bennett, P V; Sutherland, B M (1993) Quantitative detection of single-copy genes in nanogram samples of human genomic DNA. Biotechniques 15:520-5
Sutherland, B M; Bennett, P V; Conlon, K et al. (1992) Quantitation of supercoiled DNA cleavage in nonradioactive DNA: application to ionizing radiation and synthetic endonuclease cleavage. Anal Biochem 201:80-6
Kochevar, I E; Walsh, A A; Green, H A et al. (1991) DNA damage induced by 193-nm radiation in mammalian cells. Cancer Res 51:288-93
Sutherland, J C; Sutherland, B M; Emrick, A et al. (1991) Quantitative electronic imaging of gel fluorescence with CCD cameras: applications in molecular biology. Biotechniques 10:492-7
Hacham, H; Freeman, S E; Gange, R W et al. (1991) Do pyrimidine dimer yields correlate with erythema induction in human skin irradiated in situ with ultraviolet light (275-365 nm)? Photochem Photobiol 53:559-63
Sutherland, J C; Chen, C Z; Emrick, A et al. (1990) Lesion measurement in non-radioactive DNA by quantitative gel electrophoresis. Basic Life Sci 53:45-61
Hacham, H; Freeman, S E; Gange, R W et al. (1990) Does exposure of human skin in situ to 385 or 405 nm UV induce pyrimidine dimers in DNA? Photochem Photobiol 52:893-6
Sutherland, B M; Hacham, H; Gange, R W et al. (1990) DNA damage and repair in human skin: pathways and questions. Basic Life Sci 53:149-60

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