William Allen Bernhard, Ph.D.

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The use of radiation-related technologies in medical diagnostics, industrial applications, power generation, and national defense continues to grow. In each application it is necessary to weigh benefits against risk. Quantifying risk is particularly difficult in cases where radiation exposures are at a low dose rate for a long time period. Consequences of such low dose exposures are radiation-induced cancer and leukemia. In order to solve this difficult problem, radiation produced alterations in the biochemical machinery must be identified. Particularly important is the type and frequency of damage inflicted on DNA.

The aim of our research program is to fully characterize the free radical processes by which ionizing radiation, through direct effects, alters the chemical structure of DNA. The ultimate goal is to develop a set of rules that will predict the chemical damage that results when DNA is exposed to ionizing radiation.

Our approach is to use electron paramagnetic resonance (EPR) and electron nuclear double resonance (ENDOR) to study free radical processes initiated in DNA by ionizing radiation. Oligodeoxynucleotides of known sequence and predetermined crystal structure are used to investigate how the base sequence and local environment influence the distribution of electrons and holes trapped on DNA. The distribution, which effectively means the type and yield of trapped free radicals, is fundamental to understanding electron transfer, rearrangement, and radical combination reactions in DNA. The free radical reactions, ultimately terminate in stable diamagnetic damage. Using a variety of analytical tools, e.g., HPLC and NMR, stable end products are correlated with free radical precursors. Thus, we are able to discover the mechanisms by which initial ionization result in specific types of DNA damage, the damage that confronts the cells repair enzymes.

Current Appointments

• Professor - Department of Biochemistry and Biophysics (SMD)

Education
PhD Biophysics	Penn State University	1968
MS Biophysics	Penn State University	1966
BS Physics	Union College	1964

Lab Website

http://dbb.urmc.rochester.edu/labs/bernhard/index.html

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Recent Journal Articles
Showing the 5 most recent journal articles. (94 available)
Sharma, K. K.; Razskazovskiy, Y.; Purkayastha, S.; Bernhard, W. A.;. "Mechanisms of strand break formation in DNA due to the direct effect of ionizing radiation: the dependency of free base release on the length of alternating CG oligodeoxynucleotides". J Phys Chem B 113 (2009): 8183-91.
Purkayastha, S.; Milligan, J. R.; Bernhard, W. A.;. "An investigation into the mechanisms of DNA strand breakage by direct ionization of variably hydrated plasmid DNA". J Phys Chem B 112 (2008): 4152.
Sharma, K. K.; Milligan, J. R.; Bernhard, W. A.;. "Multiplicity of DNA single-strand breaks produced in pUC18 exposed to the direct effects of ionizing radiation". Radiat Res 170 (2008): 156-62.
Sharma KK; Purkayastha S; Bernhard WA. "Unaltered free base release from d(CGCGCG)2 produced by the direct effect of ionizing radiation at 4 K and room temperature." Radiation research. 2007; 167(5):501-7.
Purkayastha S; Milligan JR; Bernhard WA. "On the chemical yield of base lesions, strand breaks, and clustered damage generated in plasmid DNA by the direct effect of X rays." Radiation research. 2007; 168(3):357-66.