Cell cycle dependence of ionizing radiation-induced DNA deletions and antioxidant radioprotection in Saccharomyces cerevisiae.
The yeast DEL assay is an effective method for measuring intrachromosomal recombination events resulting in DNA deletions that when occurring in mammalian cells are often associated with genomic instability and carcinogenesis. Here we used the DEL assay to measure gamma-ray-induced DNA deletions throughout different phases of yeast culture growth. Whereas yeast survival differed by only up to twofold throughout the yeast growth phase, proliferating cells in lag and early exponential growth phases were tenfold more sensitive to ionizing radiation-induced DNA deletions than cells in stationary phase. Radiation-induced DNA deletion potential was found to correlate directly with the fraction of cells in S/G(2) phase. The ability of the antioxidants l-ascorbic acid and DMSO to protect against radiation-induced DNA deletions was also measured within the different phases of yeast culture growth. Yeast cells in lag and early exponential growth phases were uniquely protected by antioxidant treatment, whereas nondividing cells in stationary phase could not be protected against the induction of DNA deletions. These results are compared with those from mammalian cell studies, and the implications for radiation-induced carcinogenesis and radioprotection are discussed.
Hafer
Kurt
K
Departments of Radiation Oncology, Pathology, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA.
Rivina
Leena
L
Schiestl
Robert H
RH
D000975:Antioxidants / Q000494:pharmacology*; D002453:Cell Cycle / Q000528:radiation effects*; D004271:DNA, Fungal / Q000235:genetics*; D004307:Dose-Response Relationship, Radiation; D017353:Gene Deletion; D011837:Radiation-Protective Agents; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects*; D014965:X-Rays
D000975:Antioxidants; D004271:DNA, Fungal; D011837:Radiation-Protective Agents