Formation of micronuclei and of clastogenic factor(s) in patients receiving therapeutic doses of iodine-131

Ballardin, Michela; Gemignani, Federica; Bodei, Lisa; Mariani, Giuliano; Ferdeghini, M; Rossi, Anna Maria; Migliore, Lucia; Barale, Roberto

doi:10.1016/s1383-5718(01)00323-0

Cited by 40 publications

(31 citation statements)

References 40 publications

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“…Large variations in the total radioactivity measured within the two groups of our patients (treated with 3.7 and 5.5 GBq, respectively) 72 h after the application of 131-I and considerable overlap between the values measured in patients who were treated with the two different doses of 131-I could explain the lack of influence of dose on MN frequency. 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).…”

Section: Discussionsupporting

confidence: 56%

“…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.…”

Section: Discussionsupporting

confidence: 56%

“…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.…”

Section: Discussionmentioning

confidence: 99%

“…The published results showed discrepancies in the relationship between the administered 131-I activity and MN frequency. Several studies showed a dose-independent increase in MN frequency in patients with DTC treated with 131-I (Gutierrez et al 1999;Monsieurs et al 2000;Joseph et al 2009), while Ballardin et al (2002) showed a dose-dependent effect of 131-I on MN frequency. Because some of the applied iodine specifically bind and are retained in the residual thyroid tissue, while some iodine persist in other parts of the body for days after the therapy, giving very heterogeneous radiation exposure in patients treated with the same dose of 131-I (Hänscheid et al 2006(Hänscheid et al , 2009, the aim of our study was to examine whether the intensity of DNA damage measured by the cytokinesis-block micronucleus assay depends on the amount of 131-I that persists in the selected regions of interest (thyroid and abdominal region) as well as in the whole-body of DTC patients after therapy with two fixed activities (3.7 or 5.5 GBq) of 131-I.…”

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confidence: 99%

“…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.…”

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confidence: 99%

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

Vrndic

Milošević-Djordjević

Mijatovic-Teodorovic

et al. 2013

Tohoku J. Exp. Med.

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Differentiated thyroid cancers (DTCs) derive from thyroid follicular cells and include papillary and follicular cancers. In patients with DTCs, the initial treatment includes thyroidectomy and radioactive iodine (131-I) therapy. The objective of this study was to examine whether the intensity of DNA damage in peripheral blood lymphocytes (PBLs) of DTC patients depends on the amount of 131-I retained in the selected regions of interest (thyroid and abdominal region) as well as in the whole-body 72 hours after therapy. In addition, the possible influence of other factors that may affect micronuclei (MN) frequency, such as age, gender, smoking habits, and histological type of tumour was analyzed. The study population consisted of 22 DTC patients and 20 healthy donors. Data on the distribution of 131-I were obtained from the whole-body scans. MN frequency and cytokinesis-block proliferation index (CBPI) were measured using cytokinesis-block micronucleus assay. 131-I therapy significantly increased the MN frequency (19.50 ± 6.90 vs. 27.10 ± 19.50 MN) and significantly decreased the CBPI (1.52 ± 0.20 vs. 1.38 ± 0.17) in patients' lymphocytes. There was a clear correlation between the increased MN frequency and 131-I accumulation in the thyroid region in patients without metastases. The MN values did not differ in relation to the factors that could affect MN, such as age, gender, smoking habits, and histological type of tumour. In conclusion, the MN frequency in PBLs of DTC patients without metastases depends on the accumulation of 131-I in the thyroid region and does not depend on the other factors examined.

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Section: Discussionsupporting

confidence: 56%

Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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

Vrndic

Milošević-Djordjević

Mijatovic-Teodorovic

et al. 2013

Tohoku J. Exp. Med.

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Iodine-131 treatment and chromosomal damage: in vivo dose-effect relationship

Erselcan

Süngü

Özdemir

et al. 2004

European Journal of Nuclear Medicine and Molecular Imaging

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Although it is well known that radiation induces chromosomal aberrations, there is a lack of information on the in vivo dose-effect relationship in patients receiving iodine-131 treatment, and the results of previous studies are controversial. In this study, the sister chromatid exchange (SCE) method was employed to investigate acute and late chromosomal damage (CD) in the peripheral lymphocytes of 15 patients who received various doses of (131)I (259-3,700 MBq), either for thyrotoxicosis (TTX) or for ablation treatment in differentiated thyroid cancer (DTC). The SCE frequencies in cultured peripheral lymphocytes were determined before treatment (to assess basal SCE frequencies), on the 3rd day (to assess acute SCE frequencies) and 6 months later (to assess late SCE frequencies). The basal, acute and late SCE frequencies (mean+/-SD) were 3.19+/-0.93, 10.83+/-1.72 and 5.75+/-2.06, respectively, in the whole group, and these values differed significantly from each other ( P<0.001). In order to perform a quantitative evaluation of the present data and a comparative analysis with the results of previous studies reported in the literature, we defined acute and late effects using a "damage ratio" (DR) and a "recovery ratio" (RR), based on the basal, acute and late data for individual patients. No statistically significant difference was found in the DR between DTC and TTX patients (76.4%+/-11.5% vs 67.6%+/-9.0%), while the mean RR was higher in TTX patients than in the DTC group (75.2%+/-24.4% vs 36.8%+/-13.7%). The DR on the 3rd day was not related to the administered (131)I dose in the whole group, but a negative correlation was found between the (131)I dose and the RR at the 6th month (r=-0.60, P=0.04). The best fit for this relationship was obtained by a linear-quadratic model, as y=104.89x-28.4x(2)+38.1 ( R(2)=0.51, P=0.04). On the other hand, comparative analysis with the results of previous studies with comparable sampling times revealed that the best fit for the relationships between the administered dose of (131)I and DR and RR were obtained with a linear-quadratic model (Y=alpha D+beta D(2)) rather than a linear one. However, there was an interesting difference in comparison with in vitro studies, in that we found the coefficient beta to have a negative value, suggesting the disappearance of damaged lymphocytes from the peripheral circulation in a dose-dependent manner following (131)I treatment. Further studies are therefore needed to clarify the effect of the negative beta value on the biological dosimetry approach in continuous internal low LET radiation, as in the case of (131)I treatment.

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No evidence of chromosome damage in children and adolescents with differentiated thyroid carcinoma after receiving 131I radiometabolic therapy, as evaluated by micronucleus assay and microarray analysis

Federico

Boni

Fabiani

et al. 2008

Eur J Nucl Med Mol Imaging

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We demonstrated for the first time that peripheral cells of DTC children and adolescents who received (131)I at a mean dosage of 3.50 +/- 0.37 GBq did not show chromosome damage within 48 h from the end of radiometabolic therapy. This may be due to a prompt activation of the cell machinery that maintains the integrity of the genome to prevent harmful double-strand breaks from progressing to chromosome mutations, either by repairing the lesions or by eliminating the most seriously damaged cells via apoptosis.

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Formation of micronuclei and of clastogenic factor(s) in patients receiving therapeutic doses of iodine-131

Cited by 40 publications

References 40 publications

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

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

Iodine-131 treatment and chromosomal damage: in vivo dose-effect relationship

No evidence of chromosome damage in children and adolescents with differentiated thyroid carcinoma after receiving 131I radiometabolic therapy, as evaluated by micronucleus assay and microarray analysis

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