DNA Damage and Repair, Mutagenesis, and Carcinogenesis

Ph.D., Yale University, 1947
Setlow Home Page at Brookhaven National Laboratory

We have developed fish models - backcross hybrids of Xiphophorus strains - that are exquisitely sensitive to light-induced melanoma and alkylating-agent- induced retinoblastoma, presumably because the hybrids have only one tumor suppressor gene for melanoma or retinoblastoma. Physical or chemical agents may inactivate the genes by single hits and so result in tumor cell proliferation. These fish are the only useful animal models for human melanoma and retinoblastoma.

We work on the macroscopic effects of tumor induction - doses and wavelengths of light - and on the microscopic aspects - photoproduct induction and DNA sequence changes in tumor cells. The photobiological data indicate that all wavelengths tested from 302-540 nm are effective in melanoma induction, and that, even though the UVB range (290-320 nm) is most effective, the product of the effectiveness multiplied by sunlight intensity for wavelengths > 320 nm is 10 to 20-fold higher than for wavelengths < 320 nm.

Selected Publications

• Setlow, R.B., The U.S. National Research Council's view of the radiation hazards in space. Mutat. Res. 430, 169-175 (1999).
  
  
• Setlow, R.B., Spectral regions contributing to melanoma: a personal view. J. Investig. Dermatol. Symp. Proc. 4, 46-49 (1999).
  
  
• Moan, J., Dahlback, A., and Setlow, R.B., Historical Review. DNA damage and repair: A photobiological odyssey. Photochem. Photobiol. 70, 243-247 (1999).
  
  
• Setlow, R.B. Dicello, J.F., Fry, R.J.M., Little, J.B., Preston, R.J., Smathers, J.B. and Ullrich, R.L., Radiation hazards to crews of interplanetary missions: iological issues and research strategies. National Academy Press, Washington, DC, pp. 1-75 (1996).
  
  
• Setlow, R.B., Relevance of in vivo models in melanoma skin cancer. Photochem. Photobiol. 63, 410-412 (1996).
  
  
• Singer, P.T., Smalas, A., Carty, R.P., Mangel, W.F., and R.M. Sweet (1993) Locating the Catalytic Water Molecule in Serine Proteases - Response. Science 261, 621-622
  
  
• 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).
  
  
• 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).