Long-Lived Mutagenic Radicals Induced in Mammalian Cells by Ionizing Radiation are Mainly Localized to Proteins

• Published in: Radiation research 2003-07, Vol.160 (1), p.95-102
• Main Authors: Kumagai, Jun, Masui, Kiyonao, Itagaki, Yoshiteru, Shiotani, Masaru, Kodama, Seiji, Watanabe, Masami, Miyazaki, Tetsuo
• Format: Article
• Language: English
• Subjects: Albumins; Animals; Biological and medical sciences; Cell Line; Cricetinae; DNA; DNA - metabolism; DNA Damage; Dose-Response Relationship, Radiation; Electron paramagnetic resonance; Electron Spin Resonance Spectroscopy; Embryonic cells; Free Radicals; Genetic mutation; Ionizing radiation; Irradiation; Medical sciences; Mesocricetus; Mice; Microwave spectrum; Models, Chemical; Mutagens; Phenylalanine - chemistry; Radiation, Ionizing; Reactive oxygen species; REGULAR ARTICLES; Salmon; Temperature; Time Factors; Vitamin C
• ISSN: 0033-7587; 1938-5404
• DOI: 10.1667/RR3015

Kumagai, J., Masui, K., Itagaki, Y., Shiotani, M., Kodama, S., Watanabe, M. and Miyazaki, T. Long-Lived Mutagenic Radicals Induced in Mammalian Cells by Ionizing Radiation are Mainly Localized to Proteins. Radiat. Res. 160, 95–102 (2003). We have provided evidence that long-lived radicals, produced by ionizing radiation, are highly mutagenic and transforming in mammalian cells. Long-lived radicals are scavenged effectively by vitamin C or by epigallocatechin-3-O-gallate (EGCG). Long-lived radicals are not involved in lethality or in the induction of chromosome aberrations. We now report the results of experiments that define the relative amounts of long-lived radicals in DNA and proteins and identify the major protein radicals as sulfinyl radicals (R-CH2-S-O·). To make these assignments, yields of long-lived radicals in γ-irradiated salmon sperm DNA and albumin were compared by ESR. ESR spectra of long-lived radicals produced in irradiated Syrian hamster embryo (SHE) cells were analyzed precisely and compared with ESR parameters obtained by density functional theory calculations. Long-lived radicals yields of 99.8% were produced in proteins. We also identified a new type of long-lived radical as H-added phenylalanine radicals. While our evidence does not rule out the possibility of important biological consequences of the low-level long-lived radicals created by radiation, it implicates radicals in proteins as playing a key role in genetic effects of ionizing radiation. We suggest that these novel radicals, wherever they reside, need to be considered in explanations of biological sequela of radiation.