Department of Cell Stress Biology
Senior Scientist, Roswell Park Cancer Institute
Research Professor, Molecular & Cellular Biophysics, Roswell Park Division of the State University of NY Graduate School (SUNYAB)

Telephone: (716)845-3136
Fax: (716)845-8899
E-mail: harold.box@roswellpark.org

Education
Canisius College, Buffalo, NY, BS, 1948, Physics
State University of New York at Buffalo, MS, 1951, Physics
State University of New York at Buffalo, PhD, 1954, Physics

General Research Interest
My research group is investigating the nature and consequences of DNA damage, with particular interest is damage caused by oxidative stress. This type of damage occurs mainly as the inadvertent consequence of normal metabolic processes. Oxidative DNA damage is believed to be the predominant cause of mutations and is, therefore, important in the etiology of cancer. Oxidatively-induced damage is characterized initially in DNA oligomers primarily through the use of NMR spectroscopy and mass spectrometry. Subsequently, sensitive assays are designed for the detection of selected lesions in cells and tissues with the goal of measuring the level of these lesions in organisms exposed to oxidative stress. DNA oligomers containing specific identified lesions are prepared for use as substrates in measuring the competence of various DNA repair enzymes to repair the lesions. The cells of many tumors are likely deficient in repairing particular types of damage, a factor that contributes to the genetic instability of tumors. Our objective is to evaluate DNA repair as a factor in tumorigenesis.

Key Publications

 

• Paul, C.R., Belfi, C.A., Arakali, A.V. and Box, H.C. (1987) Radiation damage to dinucleoside monophosphates: Mediated versus direct damage. Int. J. Radiat. Biol. 51:103-114.
• Paul, C.R., Belfi, C.A., Arakali, A.V., and Box, H.C. ( 1987) Radiation Damage to dinucleoside monophosphates: mediated versus direct damage. Int. J. Radiat. Biol. 51, 1: 103-114.
• Paul, C.R., Wallace, J.C., Alderfer, J.L. and Box, H.C. (1988) Radiation chemistry of d(TpApCpG) in oxygenated solution. Int. J. Radiat. Biol. 54:403-415.
• Arakali, A.V., Alderfer, J.L., Paul, C.R., Belfi, C.A. and Box, H.C. (1988) Characterization of radiation and autoxidation-initiated damage in DNA model compounds. Radiat. Phys. Chem. 32:511-517.
• Paul, C.R., Arakali, A.V. and Box, H.C. (1988) Radioprotection of irradiated DNA and its model compounds. Pharma. Therapeu. 39:149-150.
• Paul, C.R., Budzinski, E.E., Maccubbin, A., Wallace, J.C. and Box, H.C. (1990) Characterization of radiation-induced damage in d(TpApCpG). Int. J. Radiat. Biol. 58:759-768.
• Maccubbin, A., Evans, M., Paul, C.R., Budzinski, E.E., Przybyszewski, J. and Box, H.C. (1991) Enzymatic excision of radiation-induced lesions from DNA model compounds. Radiat. Res. 126:21.
• Maccubbin, A.E., Evans, M.S., Budzinski, E.E., Wallace, J.C. and Box, H.C. (1992) Characterization of two radiation-induced lesions from DNA: Studies using nuclease P1. Int. J. Radiat. Biol. 61:729-736.
• Maccubbin, A.E., Budzinski, E.E., Patrzyc, H., Evans, M.S., Ersing, N. and Box, H.C. (1993) 32P-postlabeling assay for free radical-induced DNA damage: The formamido remnant of thymine. Free Rad. Res. Comms. 1:17-28.
• Maccubbin, A.E., Ersing, N., Budzinski, E.E., Box, H.C. and Gurtoo, H.L. (1994) Formation of 8-hydroxyguanine in DNA during mitomycin C activation. Biochem. Biophys. 14:1483-1491.
• Maccubbin, A.E., Przybyszewski, J., Evans, M.S., Budzinski, E.E., Patrzyc, H.B., Kulesz-Martin, M. and Box, H.C. (1995) DNA damage in UVB-irradiated keratinocytes. Carcinogenesis 16:1659-1660.
• Falcone, J.M., Shibata, M., Miller, J.H. and Box, H.C. "Catalytic Activity of Nuclease P1: Experiment and Theory". In: Radiation Damage in DNA: Structure/Function Relationships at Early Times. Fuciarelli, ed., Battelle Press, pp. 347-353, 1995.
• Falcone, J.M. and Box, H.C. (1996) Selective hydrolysis of damaged DNA by nuclease P1. Biochim. Biophys. Acta 1337:267-275.
• Budzinski, E.E., Maccubbin, A.E., Evans, M.S., Kulesz-Martin, M. and Box, H.C. (1992) Analysis of DNA damage at the dinucleoside monophosphate level: Application to the formamido lesion. Radiat. Res. 132:288-295.
• Budzinski, E.E., Maccubbin, A.E., Freund, H.G., Wallace, J.C. and Box, H.C. (1993) Characterization of the products of dinucleoside monophosphates d(GpN) irradiated in aqueous solutions. Radiat. Res. 136:171-177.
• Budzinski, E.E., Dawidzik, J.B., Wallace, J.C., Freund, H.G. and Box, H.C. (1995) The radiation chemistry of d(CpGpTpA) in the presence of oxygen. Radiat. Res. 142:107-109.
• Budzinski, E.E., Dawidzik, J.B., Rajecki, M.J., Wallace, J.C., Schroder E.A. and Box, H.C. (1997) Isolation and characterization of the products of anoxic irradiation of d(CpGpTpA). Int. J. Radiat. Biol. 71:327-336.
• Box, H.C. "Trapped Electrons in Crystals". In: Radical Ionic Systems. A. Lund and M. Shiotani, eds., Kluwer Academic Publishers, The Netherlands, pp. 409-426, 1990.
• Box, H.C., Paul, C.R. and Przybyszewski, J. (1989) Studies of radiation damage using DNA oligomers. Free Rad. Res. Comms. 6:123-126.
• Box, H.C., Budzinski, E.E. and Freund, H.G. (1990) Studies of electrons trapped in x-irradiated rhamnose crystals. Radiat. Res. 121:262-266.
• Box, H.C., Freund, H.G. and Budzinski, E.E. (1990) An unusual electron trapping site in the crystal structure of dulcitol. Radiat. Res. 122:137-141.
• Paul, C.R., Budzinski, E.E., Maccubbin, A., Wallace, J.C., and Box, H.C. (1990) Characterization of radiation-induced damage in d(TpApCpG). Int. J. Radiat. Biol. 58: 759-768.
• Beehler, B.C., Przybyszewski, J., Box, H.C. and Kulesz-Martin, M. (1992) Formation of 8-hydroxyguanosine within DNA of mouse keratinocytes exposed in culture to UVB and H2O2. Carcinogenesis 13, 11:2003-2007.
• Box, H.C., Budzinski, E.E., Evans, M.S., French, J.B. and Maccubbin, A.E. (1993b) The differential lysis of phosphoester bonds by nuclease P1. Biochim. Biophys. Acta 1161:291-294.
• Box, H.C., Budzinski, E.E., Freund, H.G., Evans, M.S., Patrzyc, H.B., Wallace, J.C. and Maccubbin, A.E. (1993a) Vicinal lesions in X-irradiated DNA? Int. J. Radiat. Biol. 3:261-263.
• Box, H.C., Freund, H.G., Budzinski, E.E., Wallace, J.C. and Maccubbin, A.E. (1995) Free radical-induced double base lesions. Radiat. Res. 141:91-94.
• Box, H.C., Schroder, E.A. and Budzinski, E.E. "The Radiation Chemistry of DNA Oligomers". In: Radiation Damage in DNA: Structure/Function Relationships at Early Times. A. Fuciarelli, ed., Battelle Press, pp. 285-290, 1995.
• Box, H.C., Budzinski, E.E., Dawidzik, J.B., Wallace, J.C., Evans, M.S. and Gobey, J.S. (1996) Radiation-induced formation of a crosslink between base moieties of deoxyguanosine and thymidine in deoxygenated solutions of d(CpGpTpA). Radiat. Res. 145:641-643.
• Box, H.C., Budzinski, E.E., Dawidzik, J.B., Gobey, J.S. and Freund, H.G. (1997) Free radical-induced tandem base damage in DNA oligomers. Free Radical Biology & Medicine 23:1021-1030.
• Box, H.C., and Maccubbin, A.E. (1997) Lipid Peroxidation and DNA Damage. Nutrition 13, 10:920-921.
• Box, H.C. "Radical Formation in Irradiated Biological Systems". In: Foundations of Modern EPR, G.R. Eaton, S.S. Eaton and K.M. Salikov (eds.), World Scientific Publishing, New Jersey, 1998.
• Box, H.C., Budzinski, E.E., Dawidzik, J.B., Wallace, J.C. and Iijima, H. (1998) Tandem lesions and other products in X-irradiated DNA oligomers. Radiat. Res. 149:433-439.