Biological toxicity of Auger emitters: molecular fragmentation versus electron irradiation.
Two hypotheses have been advanced to explain the extreme biological toxicity of DNA associated 125I: (a) high local concentrations of radiation energy from low energy Auger electron; (b) charge-induced molecular fragmentations in the DNA. To distinguish between these two hypotheses an attempt was made to evaluate the molecular events associated with electron capture decay, to calculate the microdistribution of radiation energy after 125I decay, and to relate the microdosimetry data to the biological toxicity of 125I and 3H. The cellular damage produced by the two radionuclides was evaluated on synchronized Chinese hamster ovary cells (CHO) labeled with various doses of 3H-thymidine or 125I-iododeoxyuridine. As expected, 125I (LD50: 45 rad; D0: 74 rad) proved much more toxic to CHO cells than either 3H (LD50: 380 rad; D0: 250 rad) or external X-irradiation (LD50: 330 rad; D0: 230 rad). To evaluate the molecular mechanism of 125I toxicity, iododeoxyuridine labeled with both 125I and 14C was synthesized and the effect of 125I decay on the molecular structure of iododeoxyuridine was studied by monitoring the fate of 14C activity after 125I decay. The results of this experiment indicate that 125I decay does not cause molecular fragmentation in iododeoxyuridine, only deiodination. Moreover, microdosimetry calculations show that at least in small target spheres more radiation energy is deposited on the average by decaying 125I than by a high LET alpha-particle traversing a sphere of equal diameter. These findings greatly strengthen the hypothesis that the high LET-type damage produced by Auger emitters results from high local concentrations of radiation energy rather than from charge-induced fragmentation of the DNA.
D000818:Animals; D002250:Carbon Radioisotopes / Q000009:adverse effects; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D006224:Cricetinae; D004247:DNA / Q000528:radiation effects*; D004583:Electrons; D005260:Female; D007065:Idoxuridine / Q000528:radiation effects; D007457:Iodine Radioisotopes / Q000009:adverse effects*; D010053:Ovary / Q000166:cytology; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000209:etiology*; D014316:Tritium / Q000009:adverse effects
D002250:Carbon Radioisotopes; D007457:Iodine Radioisotopes; D014316:Tritium; D004247:DNA; D007065:Idoxuridine