Gk. Livingston et al., EFFECT OF IN-VIVO EXPOSURE TO I-131 ON THE FREQUENCY AND PERSISTENCE OF MICRONUCLEI IN HUMAN-LYMPHOCYTES, Journal of toxicology and environmental health, 40(2-3), 1993, pp. 367-375
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.