Mechanistic analysis of the contributions of DNA and protein damage to radiation-induced cell death.
Protein oxidation can contribute to radiation-induced cell death by two mechanisms: (1) by reducing the fidelity of DNA repair, and (2) by decreasing cell viability directly. Previously, we explored the first mechanism by developing a mathematical model and applying it to data on  Deinococcus radiodurans . Here we extend the model to both mechanisms, and analyze a recently published data set of protein carbonylation and cell survival in  D. radiodurans  and  Escherichia coli  exposed to gamma and ultraviolet radiation. Our results suggest that similar cell survival curves can be produced by very different mechanisms. For example, wild-type  E. coli  and DNA double-strand break (DSB) repair-deficient recA-  D. radiodurans  succumb to radiation doses of similar magnitude, but for different reasons: wild-type  E. coli  proteins are easily oxidized, causing cell death even at low levels of DNA damage, whereas proteins in recA-  D. radiodurans  are well protected from oxidation, but DSBs are not repaired correctly even when most proteins are intact. Radioresistant  E. coli  mutants survive higher radiation doses than the wild-type because of superior protection of cellular proteins from radiogenic oxidation. In contrast, wild-type  D. radiodurans  is much more radioresistant than the recA- mutant because of superior DSB repair, whereas protein protection in both strains is similar. With further development, the modeling approach presented here can also quantify the causes of radiation-induced cell death in other organisms. Enhanced understanding of these causes can stimulate research on novel radioprotection strategies.
Center for Radiological Research, Columbia University Medical Center, New York, New York 10032, USA.
Igor
I
Shuryak
David J
DJ
Brenner
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D002470:Cell Survival / Q000528:radiation effects; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004260:DNA Repair; D034301:Deinococcus / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D050050:Protein Carbonylation / Q000528:radiation effects*