title: Modulation of Radiation Response by the Tetrahydrobiopterin Pathway.
abstract: Ionizing radiation (IR) is an integral component of our lives due to highly prevalent sources such as medical, environmental, and/or accidental. Thus, understanding of the mechanisms by which radiation toxicity develops is crucial to address acute and chronic health problems that occur following IR exposure. Immediate formation of IR-induced free radicals as well as their persistent effects on metabolism through subsequent alterations in redox mediated inter- and intracellular processes are globally accepted as significant contributors to early and late effects of IR exposure. This includes but is not limited to cytotoxicity, genomic instability, fibrosis and inflammation. Damage to the critical biomolecules leading to detrimental long-term alterations in metabolic redox homeostasis following IR exposure has been the focus of various independent investigations over last several decades. The growth of the "omics" technologies during the past decade has enabled integration of "data from traditional radiobiology research", with data from metabolomics studies. This review will focus on the role of tetrahydrobiopterin (BH4), an understudied redox-sensitive metabolite, plays in the pathogenesis of post-irradiation normal tissue injury as well as how the metabolomic readout of BH4 metabolism fits in the overall picture of disrupted oxidative metabolism following IR exposure.
authors.affiliation: Division of Radiation Health, Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Biomed II, Room 441A-2, 4301 West Markham #522-10, Little Rock, AR 72205, USA. RPathak@uams.edu.
authors.forename: Rupak
authors.initials: R
authors.lastname: Pathak
authors.affiliation: Department of Oncology, Georgetown University Medical Center, Washington, DC 20057, USA. Amrita.Cheema@georgetown.edu.|Department of Biochemistry, Molecular and Cellular Biology, Georgetown University Medical Center, Washington, DC 20057, USA. Amrita.Cheema@georgetown.edu.
authors.forename: Amrita K
authors.initials: AK
authors.lastname: Cheema
authors.affiliation: Department of Oncology, Georgetown University Medical Center, Washington, DC 20057, USA. smb310@georgetown.edu.|Innovation Center for Biomedical Informatics, Georgetown University Medical Center, Washington, DC 20057, USA. smb310@georgetown.edu.
authors.forename: Simina M
authors.initials: SM
authors.lastname: Boca
authors.affiliation: Division of Radiation Health, Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Biomed II, Room 441A-2, 4301 West Markham #522-10, Little Rock, AR 72205, USA. KJKrager@uams.edu.
authors.forename: Kimberly J
authors.initials: KJ
authors.lastname: Krager
authors.affiliation: Division of Radiation Health, Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Biomed II, Room 441A-2, 4301 West Markham #522-10, Little Rock, AR 72205, USA. MHJensen@uams.edu.|Surgical Service, Central Arkansas Veterans Healthcare System, Little Rock, AR 72205, USA. MHJensen@uams.edu.
authors.forename: Martin
authors.initials: M
authors.lastname: Hauer-Jensen
authors.affiliation: Division of Radiation Health, Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Biomed II, Room 441A-2, 4301 West Markham #522-10, Little Rock, AR 72205, USA. NAykinBurns@uams.edu.
authors.forename: Nukhet
authors.initials: N
authors.lastname: Aykin-Burns
keywords: ionizing radiation; metabolomics; oxidative stress; tetrahydrobiopterin