EFFECT OF IN-VIVO EXPOSURE TO I-131 ON THE FREQUENCY AND PERSISTENCE OF MICRONUCLEI IN HUMAN-LYMPHOCYTES

The validity of the micronucleus test as a biomarker of chromosome dam age in dividing mammalian cells is well established, This assay was us ed to study the response of peripheral lymphocytes of a 34-yr-old male patient following treatment with I-131 ablative radiation therapy fol lowing a total thyroidectomy. Coincidentally, 8 mo before diagnosis, t he patient had provided a blood sample for an in vitro study of micron ucleus induction following exposure to graded doses of x-rays. The bac kground frequency in the unexposed culture showed a mean count of 6.0 micronuclei per 1000 binucleated (first division) lymphocytes, while m ean values of 18.5, 29.0, 41.0, 61.0 and 75.5 micronuclei/1000 cells w ere observed following x-ray doses of 5, 10, 15, 20, and 25 cGy, respe ctively. These data fit a nonthreshold, linear dose-response function (y = 2.78x + 3.71; r = .99). Eight months after the in vitro x-ray stu dy, the subject was diagnosed with thyroid cancer. Surgery was perform ed, and 5 wk later the patient received 1.78 GBq (48 mCi) of I-131 as adjuvant radiation therapy. Blood was drawn 11 d after the radiation t reatment 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-r esponse equation from the earlier study, the sixfold increase in micro nucleus frequency suggests a dose to the peripheral blood of approxima tely 11 cGy. The cytogenetic dose estimate compares to approximately 3 0 cGy using a new mode/based on external whole-body counting data. Nin e 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 sa mple. Data show that radiation-induced cellular lesions persist for mo nths following relatively brief radiation exposure to a medical isotop e. Results of this study support the conclusion that the lymphocyte mi cronucleus test is a rapid, sensitive, and perhaps quantitative biomar ker of low-dose (<25 cGy) radiation exposure.