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

Abstract

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.

Micronucleus frequency among Iraqi thyroid disorder patients

“…This possibility is supported by the genotoxicity associated with radiations which were observed by several studies. Such studies have investigated the level of genome damage and micronucleus in thyroid cancer patients environmentally exposed to radiation after the Chernobyl fallout (Sbrana et al 2006; Tronko et al 2007; Cardis and Hatch 2011), after Fukushema in Japan (Medalia 2011), in patients affected by thyroid cancer who underwent radiotherapy (Livingston et al 1993; Gutierrez et al 1997, 1999; Dardano et al 2007; Hooman et al 2008), and in people affected by thyroid nodules following occupational exposure to ionizing radiation (Brooks et al 2007; Scarpato et al 2009). …”

Correlation between Micronuclei Frequency in Peripheral Blood Lymphocytes and Retention of 131-I in Thyroid Cancer Patients

“…The dose-independent increases of MN frequency in PBLs of DTC patients treated with 131-I were reported by Gutierrez et al (1999), Monsieurs et al (2000), and Joseph et al (2009), while Ballardin et al (2002) showed a dose-dependent effect of 131-I on MN frequency. Previous studies show an increased DNA damage in the PBLs of DTC patients treated with 131-I (Livingston et al 1993;Watanabe et al 1998;Ballardin et al 2002;Hooman et al 2008). However, our study is the first to examine whether the frequency of MN in the PBLs of radioiodine-treated DTC patients depends on the retention of radioiodine in the selected parts, as well as in whole patient's body after the therapy.…”

“…The blood is irradiated by β-particles emitted from circulating 131-I and from penetrating γ-radiation, originating from the activity dispersed throughout the body (Lassmann et al 2010). In PBLs of 131-I-treated patients chromosomal aberrations (BaugnetMahieu et al 1994;Gundy et al 1996;Monteiro et al 2000;Puerto et al 2000), the MN frequency (Livingston et al 1993;Watanabe et al 1998;Ballardin et al 2002;Lee et al 2002;Hooman et al 2008) and the CBPI (Gutirrez et al 1995;Ramirez et al 1997) were analyzed.…”

“…MN are chromosomal fragments or whole chromosomes not included in the nuclei during division but present in the cytoplasm of daughter cells as small additional nuclei (Fenech et al 2011). Numerous published studies showed an increase of MN frequency in PBLs of DTC patients treated with 131-I (Livingston et al 1993;Watanabe et al 1998;Ballardin et al 2002;Hooman et al 2008). The published results showed discrepancies in the relationship between the administered 131-I activity and MN frequency.…”

Nuclear Abnormalities of Lymphocytes as the Simplest Markers for Bioindication Test in Case of Mass Casualty Events Involving Radiation Exposure

“…The presented microphotographs were obtained by us in 1994 from the archive of hematological samples taken from the liquidators of Chernobyl disaster [23]. Livingston et al [24] demonstrated that the relationship between the frequency of detection of micronuclei and the radiation dosage is described by a non-threshold linear function: y= 2.78x + 3.71. This formed the basis for the widespread micronucleus test [17,25], validated in ionizing radiation biodosimetry.…”