PARENT SESSION

Mutagenesis/Clastogenesis/Carcinogenesis

(PP086) Mutagenicity of fractionated radiations.

Ueno, Akiko^{*,1, 2}, Vannais, Diane², Waldren, Charles³, ¹ National Institute of Radiological Sciences, Chiba, Japan, Japan² Environmental & Radiological Health Sciences, Fort Collins, CO, USA³ Radiation Effects Research Foundation (RERF), Hiroshima/Nagasaki, Japan, Japan

ABSTRACT- Since radiation therapy is often administered in fractions of 2 Gy/day we compared the lethality, mutagenicity and mutant spectrum of this exposure regimen vs. the same total doses given acutely, without and with daily medium changes. Measurements were made in the human-hamster AL hybrid cell/CD59 assay system in which mutation is uncoupled from lethality so that CD59^- mutants ranging from a few bases to more than 133 Mbp can be quantified. Irradiations were with a JL Shepherd Mark 1/68A model 137Cs- irradiator at a dose rate of 1.7 Gy/min at room temperature. We found that fractionated doses were less lethal than equivalent single doses, significantly so at 8 Gy or more. Cell killing was unaffected by media changes. If media were not changed, acute and fractionated doses were equally mutagenic whereas changing the media reduced mutant yields by about half,indicating creation by radiation of mutagenic but not lethal factors in medium. As for mutant spectra, about 30 fold more of the CD59^- mutants recovered from the fractionation protocol displayed characteristics of genomic instability than mutants from a single dose. Note, however, that mutant spectra were measured at the peak of mutant induction, 10 Gy and 3 Gy for fractionated doses and acute doses, respectively, not at equitoxic doses. We do not imply that these in vitro results should have immediate impact on well established and effective therapy protocols, only to point out that mutagenic, and thus potentially carcinogenic outcomes like generation of genomic instability can be affected by the delivery regimen which could have implications for long-term therapy outcome, especially for younger patients where secondary tumors are a serious consideration.

Key words: fractionation, genomic instability, mutant spectra, media effects