DNA lesion complexity and induction of apoptosis by ionizing radiation.
OBJECTIVE
To determine whether murine lymphoid cell lines can discriminate between high- and low-LET (linear energy transfer) radiation-induced DNA lesions.


METHODS
Sensitivity to killing by DNA-incorporated 3H and 125I decays, accumulated during storage in the gas phase of a liquid nitrogen tank, was determined by clonogenic survival assay.


RESULTS
Induction of a lethal event in the STRij-4-2.2, WEHI-22.1, and L5178Y-R cell lines required approximately 30 times more 3H than 125I decays. Hence, the same ratio of 3H to 125I decays was found irrespective of whether the cell lines contained mutant or wild-type p53 and irrespective of whether they underwent rapid interphase or mitosis-related apoptosis after irradiation. The 18-81 cell line differed in showing a ratio of around 21 and it is argued that this may be a consequence of v-ABL over-expression. The assumption that DNA-incorporated 3H and 125I decays are low- and high-LET-like events respectively was confirmed by the similar sensitivity of L5178Y-R and -S cells to killing by 125I decays in contrast with their difference in sensitivity to 3H decays.


CONCLUSIONS
The difference in lethal effectiveness between DNA-incorporated 3H and 125I decays can be explained by the hypothesis that simple DSB (double-strand breaks) are non-lethal and that cell killing is attributable to complex DSB. The low-LET radiation-specific sensitization of L5178Y-S cells may reflect defective repair of a DNA lesion class (presumably simple DSB) that is differentially induced by high- and low-LET radiation and is non-lethal to cells with normal repair capacity.
Radford
I R
IR
Peter MacCallum Cancer Institute, St Andrews Place, East Melbourne, Victoria 3002, Australia. i.radford@pmci.unimelb.edu.au
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects*; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D003114:Colony-Forming Units Assay; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair; D016313:Genes, abl; D016158:Genes, p53 / Q000528:radiation effects; D007457:Iodine Radioisotopes; D018499:Linear Energy Transfer; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D051379:Mice; D009154:Mutation; D014170:Transformation, Genetic; D014316:Tritium
D007457:Iodine Radioisotopes; D014316:Tritium; D004247:DNA