Long-lived mutagenic radicals induced in mammalian cells by ionizing radiation are mainly localized to proteins

Radiat Res. 2003 Jul;160(1):95-102. doi: 10.1667/rr3015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cricetinae
  • DNA / metabolism
  • DNA Damage
  • Dose-Response Relationship, Radiation
  • Electron Spin Resonance Spectroscopy
  • Free Radicals
  • Mesocricetus
  • Mice
  • Models, Chemical
  • Mutagens*
  • Phenylalanine / chemistry
  • Radiation, Ionizing*
  • Salmon
  • Temperature
  • Time Factors

Substances

  • Free Radicals
  • Mutagens
  • Phenylalanine
  • DNA