Persistent genetic damage in blood and bone marrow cells following radioiodine therapy

Patients treated with medical isotopes provide opportunity for prospective study of radiation effects induced by internally-deposited radionuclides. We analyzed serial blood samples of a thyroid cancer patient treated with 131I for changes in micronuclei (MN) and chromosome aberrations (CA) in lymphocytes and glycophorin A (GPA) locus mutations in erythrocytes. Initial treatment (48 mCi) induced a 6-fold increase in MN frequency (from 6 to 36/1000). Dose response studies of the patient's lymphocytes X-irradiated in vitro before diagnosis of cancer showed the increase corresponds to an in vivo blood dose of 11.4 cGy compared to an NCRP red marrow dose estimate of 9.6 cGy (0.2 cGy/mCi 131I). A second treatment (390 mCi), given 26 months after the first, further increased the MN frequency to 17-fold over background (101/1000). Analysis of 80 MN for kinetochores using the CREST anti-kinetochore antibody showed that 90% contained acentric chromosomal fragments. Analysis of 100 G-banded metaphases revealed 20 with structural CAs including rings, deletions, translocations and a dicentric. The frequency of GPA allele-loss variant erythrocytes increased from 11.4 to 10.8 and 17.8 x 10-6 in samples obtained at 2, 4 and 6 months, respectively, after the second treatment. This response is consistent with radiation-induced GPA mutations in long-lived erythroid marrow stem cells as previously reported for A-bomb survivors. The induced frequency of GPA variant cells corresponds to a red marrow dose of 60 cGy based on the persistent linear dose response of 25 x 10-6 per Gy from previous studies. We conclude that exposure to 131I induces persistent genetic damage and that these biodosimetric methods are useful in reconstructing radiation doses in exposed individuals