title: Long-lived mutagenic radicals induced in mammalian cells by ionizing radiation are mainly localized to proteins.
abstract: 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 gamma-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.
authors.affiliation: Department of Applied Chemistry, Graduate School of Engineering, Nagoya University, Furo-Cho, Chikusa-ku, Nagoya 464-8603, Japan. kumagai@apchem.nagoya-u.ac.jp
authors.forename: Jun
authors.initials: J
authors.lastname: Kumagai
authors.forename: Kiyonao
authors.initials: K
authors.lastname: Masui
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Itagaki
authors.forename: Masaru
authors.initials: M
authors.lastname: Shiotani
authors.forename: Seiji
authors.initials: S
authors.lastname: Kodama
authors.forename: Masami
authors.initials: M
authors.lastname: Watanabe
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Miyazaki
mesh_terms: D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D008647:Mesocricetus; D051379:Mice; D008956:Models, Chemical; D009153:Mutagens; D010649:Phenylalanine / Q000737:chemistry; D011839:Radiation, Ionizing; D012474:Salmon; D013696:Temperature; D013997:Time Factors
chemical_list: D005609:Free Radicals; D009153:Mutagens; D010649:Phenylalanine; D004247:DNA