Effect of in vivo exposure to iodine-131 on the frequency and persistence of micronuclei in human lymphocytes.

The validity of the micronucleus test as a biomarker of chromosome damage in dividing mammalian cells is well established. This assay was used to study the response of peripheral lymphocytes of a 34-yr-old male patient following treatment with 131I ablative radiation therapy following a total thyroidectomy. Coincidentally, 8 mo before diagnosis, the patient had provided a blood sample for an in vitro study of micronucleus induction following exposure to graded doses of x-rays. The background frequency in the unexposed culture showed a mean count of 6.0 micronuclei per 1000 binucleated (first division) lymphocytes, while mean values of 18.5, 29.0, 41.0, 61.0 and 75.5 micronuclei/1000 cells were observed following x-ray doses of 5, 10, 15, 20, and 25 cGy, respectively. These data fit a nonthreshold, linear dose-response function (y = 2.78x + 3.71; r = .99). Eight months after the in vitro x-ray study, the subject was diagnosed with thyroid cancer. Surgery was performed, and 5 wk later the patient received 1.78 GBq (48 mCi) of 131I as adjuvant radiation therapy. Blood was drawn 11 d after the radiation treatment and at monthly intervals thereafter to analyze the frequency and persistence of micronuclei. The first posttreatment sample showed 35.5 micronuclei per 1000 binucleate cells. Based on the linear dose-response equation from the earlier study, the sixfold increase in micronucleus frequency suggests a dose to the peripheral blood of approximately 11 cGy. The cytogenetic dose estimate compares to approximately 30 cGy using a new model based on external whole-body counting data. Nine consecutive monthly samples have been analyzed to date. Although the micronucleus count has fluctuated (four- to sixfold above background), the frequency after 8 mo is equivalent to the first posttreatment sample. Data show that radiation-induced cellular lesions persist for months following relatively brief radiation exposure to a medical isotope. Results of this study support the conclusion that the lymphocyte micronucleus test is a rapid, sensitive, and perhaps quantitative biomarker of low-dose (< 25 cGy) radiation exposure.