Richard B. Setlow
Senior Biophysicist Emeritus,
Member of the National Academy of Sciences

Biology Department, Bldg. 463
Brookhaven National Laboratory
Upton, NY 11973-5000

Research Interests:

We do research on DNA damages, DNA repair, mutagenesis and carcinogenesis. We have developed a fish model - a backcross hybrid of Xiphophorus strains - that are exquisitely sensitive to light-induced melanoma, presumably because the hybrids have only one tumor suppressor gene for melanoma. Single, acute exposures to monochromatic light of wavelengths between 302-540 nm inactivate the gene and result in melanomas. These fish are the only useful model for human melanoma. Extrapolation of the data to sunlight exposures indicates that the most effective wavelengths are >320 nm. Such wavelengths are not significantly attenuated by sunscreens. We suspect that black pigment melanin acts as a photosensitizer and results in photoproducts in DNA that inactivate the suppressor gene. We are attempting to identify the photoproducts in light-exposed human melanoma cells containing melanin.

In collaboration with Marine Scientists at SUNY, Stony Brook, and the University of Georgia, we used transgenic medaka fish (Oryzias latipes) to find the presence of mutagenic compounds in sediments around Long Island Sound. We collaborate with Japanese scientists to assess the mutagenic potential of high atomic number, high energy nuclei in cosmic rays. These nuclei pose a risk to astronauts traveling beyond low Earth orbits.

Dick Setlow is a member of the National Academy of Sciences and has received prestigious awards from the Comité International de Photobiologie, the Department of Energy, and the Enviromnental Mutagen Society. After 12 years as Associate Director and 2 years as Acting Associate Director for Life Sciences as well as 7 years as Chairman of the Biology Department, Dick returned to more active research in 1998. See the story in the Brookhaven Bulletin Vol.52 No.30 of July 31, 1998. Results of recent work on the effects of cosmic radiation on spacetravelers are reported in a 2005 publication and are summarized in the BNL Press Release of April 14, 2005: 'Astronauts' Children Unlikely to Inherit Cosmic Ray-Induced Genetic Defects'. The most recent work, PNAS (Jan.15,2008), shows that increased sun exposure may lead to improved cancer prognosis as a result of Vitamin D synthesis rather than skin cancer incidence

Selected References:

 A hybrid Xiphophorus
with melanoma on dorsal fin.
The fish is about 3cm long.
Moan J., Porojinicu A.C., Dahlback A. and Setlow R.B.
Addressing the health benefits and risks, involving vitamin D or skin cancer, of increased sun exposure.
Proc Natl Acad Sci USA 105(2): 668-673 (2008).  PubMed
Wood S.R., Berwick M., Ley R.D., Walter R.B., Setlow R.B. and Timmins G.S.
UV causation of melanoma in Xiphophorus is dominated by melanin photosensitized oxidant production.
Proc Natl Acad Sci USA 103: 4111-4115 (2006).  PubMed
Shimada A., Shima A., Nojima K., Seino Y. and. Setlow R.B
Germ cell mutagenesis in medaka fish after exposures to high-energy cosmic ray nuclei: A human model.
Proc Natl Acad Sci USA 102(17): 6063-6067 (2005).   PubMed
Setlow R.B.
Historical Reflections: A second life in science--working after the age of 65.
DNA Repair (Amst) 3(4): 441-449 (2004).   PubMed
Setlow R.B.
Shedding light on proteins, nucleic acids, viruses, cells, humans and fish.
Mutat Res 511: 1-14 (2002).   PubMed
Setlow R.B.
The U.S. National Research Council's view of the radiation hazards in space.
Mutat Res 430: 169-175 (1999).   PubMed
Setlow R.B.
Spectral regions contributing to melanoma: a personal view.
J Investig Dermatol Symp Proc. 4: 46-49 (1999).   PubMed
Setlow R.B.
Historical Review. DNA damage and repair: A photobiological odyssey.
Photochem Photobiol. 65S: 1195-1225 (1997).
Setlow R.B.
Relevance of in vivo models in melanoma skin cancer.
Photochem Photobiol. 63: 410-412 (1996).   PubMed
Bender M.A. and Setlow R.B.
Distributions of spontaneous chromosomal aberrations and of spontaneous and induced SCE and micronuclei in peripheral lymphocytes from a human population.
in: Proc Second Intl Symp on Chromosomal Aberrations (AT Natarajan and G Obe, edts) pp 280-290, Springer Verlag, Berlin, Germany (1994).
Setlow R.B., and Woodhead A.D.
Temporal changes in the incidence of malignant melanoma: explanation from action spectra.
Mutat. Res. 307: 365-374 (1994).   PubMed
Setlow R.B., Grist E., Thompson K. and Woodhead A.D.
Wavelengths effective in induction of malignant melanoma.
Proc Natl Acad Sci USA 90: 6666-6670 (1993).   PubMed   Full Text (pdf)
Ban S., Setlow R.B., Bender M.A., Ezaki H., Hiraoka T., Yamane M., Nishiki M., Dohi K., Awa A.A., Miller R.C., Parry D.M., Mulvihill J.J. and Beebe G.W.
Radiosensitivity of skin fibroblasts from atomic bomb survivors with and without breast cancer.
Cancer Research 50: 4050-4055 (1990).   PubMed
Hart RW, RB Setlow, and AD Woodhead.
Evidence that pyrimidine dimers in DNA can give rise to tumors.
Proc Natl Acad Sci USA 74, 5574-5578 (1977).   PubMed   Full Text (pdf)
Setlow RB, and WC Carrier.
The disappearance of thymine dimers from DNA: An error-correcting mechanism.
Proc Natl Acad Sci USA 51, 226-231 (1964).   PubMed   Full Text (pdf)

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