Influence of DNA-repair gene variants on the micronucleus frequency in thyroid cancer patients.

The role of different DNA-repair genes (OGG1, XRCC1, XRCC2 and XRCC3) on both the spontaneous and the induced frequency of micronuclei (MN) has been studied in the lymphocytes of a group of 114 patients with differentiated thyroid cancer (DTC). Induction of MN was achieved by treatment of the lymphocytes with 0.5Gy of gamma-radiation. The selected genes are involved in base-excision repair (BER) (OGG1, Ser326Cys; XRCC1, Arg280His and Arg399Gln), and in homologous recombination repair (HRR) (XRCC2, Arg188His and XRCC3, IVS5-14G). Genotyping was carried out by use of the iPLEX (Sequenom) technique. Results indicate that only the OGG1-Ser326Cys polymorphism was able to modulate the MN frequency. This effect was only observed in the spontaneous MN frequency (P=0.016), but not in the MN frequency induced after irradiation. In addition, a strong correlation was observed between spontaneous and induced MN frequency, which would suggest an underlying genetic background.

Comparative study of whole-body MRI and bone scintigraphy for the detection of bone metastases.

AIM: To assess and compare the diagnostic accuracy of whole-body magnetic resonance imaging (MRI) and bone scintigraphy in the detection of metastases to bone. MATERIAL AND METHODS: Forty randomly selected patients with known malignant tumours were prospectively studied using bone scintigraphy and whole-body MRI. Two patients were excluded. Symptoms of bone metastasis were present in 29 (76%) patients and absent in nine (24%). Findings were classified into four categories according to the probability of bone metastasis: (1) negative, (2) probably negative, (3) probably positive, and (4) positive. Diagnostic accuracy was determined according to the area under the receiver operating characteristic (ROC) curve. The definitive diagnosis was reached using other imaging techniques, biopsy, or 12 months clinical follow-up. RESULTS: Metastases were present in 18 patients. The sensitivity, specificity, and diagnostic accuracy were 94, 90, and 92%, respectively, for whole-body MRI and 72, 75, and 74%, respectively, for bone scintigraphy. Diagnostic accuracy measured by the area under the ROC curve was significantly higher for whole-body MRI (96%) than for bone scintigraphy (77%; p<0.05). Interobserver agreement measured by the kappa index was significantly higher for whole-body MRI (0.895) than for bone scintigraphy (0.524; p<0.05). Whole-body MRI detected lesions in tissues other than bone in 17 (45%) patients. CONCLUSIONS: Whole-body MRI is more accurate and more objective than bone scintigraphy for the detection of bone metastases. Whole-body MRI can also detect lesions in tissues other than bone.

Role of GST and NAT2 polymorphisms in thyroid cancer.

Genetic polymorphisms have shown to be susceptibility factors playing an important role in the development of most cancers. Nevertheless, as far as we know, only few studies have been conducted linking thyroid cancer incidence and GST polymorphisms, and no data are available on the possible association between NAT2 polymorphisms and thyroid cancer risk. The possible relationship between polymorphism at the GSTM1, GSTT1, GSTP1, and NAT2 genes and increased susceptibility to thyroid cancer has been evaluated in 176 thyroid cancer patients and 167 healthy controls, all from the urban district of Barcelona (Spain). The results indicate a clear role of the C481T change, present in several NAT2*5 alleles [odds ratio (OR)=0.58; 95% confidence interval (95% CI)=0.35-0.98]. Thus, those individuals carrying this change are less prone to develop thyroid cancer, mainly of the papillary type. In addition, there is a tendency towards the over-representation of the GSTM1 null genotype among thyroid cancer patients, particularly in those patients with papillary type tumor. The same is observed for the GSTM1 and GSTT1 null genotypes combination, and for other combinations with different NAT2 polymorphisms. The combinations involving the NAT2*6 and NAT2*7 genotypes showed the most important effect, and individuals carrying both alleles present a higher risk of thyroid cancer (OR=7.36; 95% CI=0.85-63.47), mainly for the follicular type (OR=17.94; 95% CI=1.34-238.70). The combination of NAT2*5 with NAT2*7 was also found to increase 5.26 (95% CI=1.07-25.76) times the risk of thyroid cancer. In conclusion, our results show that NAT2 polymorphisms play a significant role in thyroid cancer risk modulation.

Asymptomatic bilateral adrenal pheochromocytoma in a patient with a germline V804M mutation in the RET proto-oncogene.

UNLABELLED: A diagnosis of bilateral pheochromocytoma warrants exclusion of hereditary pheochromocytoma. OBJECTIVE: To describe the first case of a bilateral pheochromocytoma associated with V804M mutation in the RET proto-oncogene. PATIENTS: The index case was a 54-year-old man with bilateral adrenal masses discovered during a CT scan performed for other reasons. MEASUREMENTS: Genetic analysis included exons 8-11 and 13-17 in the RET proto-oncogene, all four exons and flanking intronic regions in the SDHD gene, all eight exons and flanking intronic regions in the SDHB, and all three exons in the VHL gene. RESULTS: Investigations revealed elevated urinary metanephrines (32.3 micromol/day), and laparoscopic bilateral adrenalectomy confirmed bilateral pheochromocytomas. A heterozygous V804M mutation in exon 14 of the RET was found in the index case and in four relatives. Total thyroidectomy, performed in four of five affected members in this kindred, disclosed a medullary thyroid carcinoma in the index case and in a 50-year-old woman, and nodular C-cell hyperplasia in the other two subjects. CONCLUSIONS: This clinical case suggests that individuals carrying the germline V804M mutation should be screened annually for the presence of pheochromocytoma.

[Thyroid carcinoma:Experience 57 cases. Is there a different bio-development in pediatric age?]. / Carcinoma de tiroides: experiencia de 57 casos. Distinto biodesarrollo en la edad infantil?

UNLABELLED: It has been suggested a different biodevelopment in the differentiated thyroid cancer in pediatric age. General and pediatric surgeons from different centres has coincided to operate this kind of pediatric pathology that finally conclude the treatment in the nuclear medicine department from the reference hospital. The objectives of this revision is, to confirm de difference in thyroid cancer in pediatric age and to know few factors implicated. MATERIALS AND METHODS: A review of 57 patients with differentiated thyroid cancer, medullary and anaplastic were excluded, treated in the nuclear medicine department during the last 20 years. 28% were < 10 years old (16 cases) and 72% > 10 years old (41 cases). This 57 young patients were operated in 22 hospitals and 79% by a general surgeon and 21% by pediatric surgeon. The analysis was performed with SPSS MS Windows 6.0 (chi cuadrado, t-Student-Fisher). RESULTS: There are more reinterventions in patients operated by a general surgeon. There aren't differences between the number of total neck dissections between both groups of surgeons, but when is performed, the incidence of complications is significantly high. In patients < 10 years old, there are more metastasis and more surgical complications. In spite of, all patients still alive. CONCLUSIONS: Children < 10 years old, the illness is more local aggressive and the recurrence and lung metastasis is high, more surgical complications. We recommend to concentrate this pathology in a few hospitals to achieve more experience and to avoid complications.

Carcinoma de tiroides: experiencia de 57 casos. ¿Distinto biodesarrollo en la edad infantil? / Thyroid carcinoma: experience 57 cases. Is there a different biodevelopment in pediatric age?

Se ha sugerido un biodesarrollo distinto del carcinoma diferenciado de tiroides en la edad infantil. Cirujanos generales y pediá-tricos de distintos centros han coincidido en intervenir este tipo de patología pediátrica que finalmente terminan su tratamiento en el servicio de medicina nuclear del hospital de referencia. El objetivo de nuestro trabajo es confirmar las diferencias en el carcinoma de tiroidesinfantil y establecer los factores implicados. Material y métodos. Hemos revisado 57 pacientes afectos de carcinoma diferenciado de tiroides excluyendo las formas medular y anaplásica, tratados en el Servicio de Medicina Nuclear, en los últimos 20años. El 28% eran < 10 años (16 casos) y el 72% > 10 años (41 casos).Estos 57 niños fueron intervenidos quirúrgicamente en 22 hospitales el 79% por cirujanos generales y el 21% por cirujanos pediátricos. El análisis de los datos se ha realizado con SPSS MS Windows 6.0 (chicuadrado, t-Student-Fisher).Resultados. Hay significativamente más reintervenciones en los pacientes operados por los cirujanos generales. Cuando se realiza vaciamiento ganglionar la incidencia de complicación es significativamente más alta. En los pacientes < de 10 años, hay una mayor (..) (AU)

nm23-H1 immunoreactivity as a prognostic factor in differentiated thyroid carcinoma.

Several prognostic factors have been proposed to identify the patients at risk to develop metastases in differentiated thyroid carcinoma. Reduced nm23-H1 expression (a metastatic suppressor gene) has been correlated with high tumor metastatic potential in various human carcinomas, but the results obtained in differentiated thyroid carcinoma remain controversial. To elucidate the usefulness of nm23-H1 as a differentiated thyroid carcinoma prognosis factor, we evaluate the relationship between nm23-H1 immunoreactivity as well as both clinical status and patient outcome. For this purpose, thyroid resected specimens obtained from 94 differentiated thyroid carcinoma consecutive patients (64 papillary and 30 follicular) with at least 5 yr of follow-up were stained using monoclonal antibody to nm23-H1. We did not observe any relationship between nm23-H1 immunoreactivity and age, gender, initial differentiated thyroid carcinoma stage, local recurrence, or distant metastases in patients with papillary carcinoma. However, in patients with follicular carcinoma, a significant inverse association between metastatic disease and the expression of nm23-H1 product was obtained (P < 0.05). In addition, significant differences were found in the survival curves according to nm23-H1 immunoreactivity (log-rank P < 0.01). Finally, nm-23-H1 immunoreactivity was more specific but less sensitive than AMES score to predict metastases. In conclusion, our results suggest that nm23-H1 immunostaining could be added to the classic prognostic factors currently used to predict the outcome of patients with follicular thyroid carcinoma.

Salivary and lacrimal gland dysfunction (sicca syndrome) after radioiodine therapy.

UNLABELLED: Salivary gland dysfunction has been described in patients undergoing radioiodine therapy but associated lacrimal gland dysfunction (sicca syndrome) has never been reported. We conducted a prospective cohort study with follow-up for up to 3 y in a tertiary care university center to determine the prevalence of sicca syndrome in patients after high-dose radioiodine treatment. METHODS: From January 1990 to December 1995, all patients undergoing radioiodine therapy (n = 79) with a standard dose of 925 MBq to 18.5 GBq (25-500 mCi) were interviewed using a standardized questionnaire to determine subjective ocular and oral dryness and were examined for objective lacrimal and salivary gland dysfunction. RESULTS: After radioiodine treatment, 32.9% of the patients reported subjective xerostomia and 25.3% reported subjective xerophthalmia in the first year of follow-up. Xerostomia persisted to the second year of follow-up in 20.3% of cases and was still present >3 y after the last dose of radioiodine in 15.2% of cases. Xerophthalmia persisted to the second year of follow-up in 17.7% of cases and was still present in the third year of follow-up in 13.9% of cases. Severe xerostomia occurred in 4 patients. Reduced salivary and lacrimal gland function was documented in 40 (50.6%) and 14 (17.7%) of the 79 cases, respectively, in the first year of follow-up. Objective xerostomia persisted in 13.9% of cases to the second year of follow-up and was still present in all patients >3 y after the last radioiodine application. Keratoconjunctivitis sicca persisted in 11 patients (13.9%) to the second year of follow-up but was only present in 6 patients (7.6%) >3 y after the last radioiodine application. Additionally, 28/79 patients (35.4%) who had a normal salivary gland scintigraphy previously showed reduced salivary gland function in the third year of follow-up. No significant dependence on cumulative treatment was found for objective xerostomia or xerophthalmia, but doses >11.1 GBq (300 mCi) were related to stage 3 dysfunction on salivary gland scintigraphy. CONCLUSION: Salivary and lacrimal gland dysfunction (sicca syndrome) is relatively frequent after radioiodine therapy. In most cases this is a transient side effect, but in some patients it may persist for a long period or appear late.

Equal induction and persistence of chromosome aberrations involving chromosomes 1, 4 and 10 in thyroid cancer patients treated with radioactive iodine.

A number of in vitro studies have questioned the assumption of random distribution of breaks in radiation-induced chromosome aberrations. The therapeutic application of radioactive 131I in thyroid cancer patients offers a good opportunity to study the induction and persistence of cytogenetic damage involving different chromosomes in vivo. Using whole-chromosome painting probes and triple colour painting by fluorescence in situ hybridization (FISH), we have analysed the frequency of chromosomal aberrations (CAs) involving chromosomes 1, 4 and 10 in peripheral blood lymphocytes of 10 thyroid cancer patients sampled before and 1 week, 1 year and 3.5 years after therapeutic application of radioactive iodine in a self-controlled, longitudinal study. A highly significant 3.4-fold increase in the frequency of chromosome breaks was observed 1 week after treatment with a similar representation of all chromosomes analysed. Although a significant decrease in dicentrics was observed during the first year after treatment, the frequency of chromosome aberrations remained over control levels until the last sampling time, 41-47 months post-treatment. The same behaviour, in terms of induction and persistence, was observed for all three chromosomes, confirming our previous results in vitro and rejecting the reported suggestion that chromosome 10 is radiosensitive in vivo. Our finding that the dynamics of radiation-induced CA in vivo is independent on the chromosome of choice suggests that this variable is not important in retrospective studies.

Multicolour FISH detection of radioactive iodine-induced 17cen-p53 chromosomal breakage in buccal cells from therapeutically exposed patients.

Simultaneous labelling of 17cen and the p53 locus by multicolour FISH was used to monitor radioactive iodine-induced structural and numerical chromosome abnormalities in buccal cells from 29 hyperthyroidism and thyroid cancer patients sampled before and after therapeutic treatment. This novel methodology allowed the efficient detection of 17p deletions leading to p53 allelic deletions, 17p gains and whole chromosome 17 numerical abnormalities in epithelial cells. Highly significant increases in the frequency of cells with (i) 17p abnormalities (1.8-fold; P < 0.001), including p53 monoallelic deletions (2.1-fold; P < 0.001) and 17p gains (3.5-fold; P < 0.001); (ii) chromosome 17 numerical abnormalities (2-fold; P < 0.001); and (iii) simultaneous 17p breakage and chromosome 17 numerical abnormalities (2.3-fold; P < 0.001), were observed after radioactive iodine treatment. As expected, the major contribution to these increases was detected in hyperthyroidism patients compared with thyroid cancer patients who suffered thyroidectomy before radioactive iodine exposure and, therefore, experienced a rapid elimination of the radioisotope. Considering that both the genetic endpoints and the target tissue are extremely relevant in carcinogenesis, it is suggested that the observed genetic damage could contribute to the reported increase in cancer risk of people therapeutically or accidentally exposed to radioactive iodine.

[Diagnostic performance of serum thyroglobin and iodide-131 Na scan according to the type of recurrence in differentiated thyroid carcinoma]. / Rendimiento diagnóstico de la determinación plasmática de tiroglobulina y del rastreo corporal con 131INa según el tipo de recurrencia en el carcinoma diferenciado de tiroides.

BACKGROUND: There is no consensus about the best follow-up protocol in differentiated thyroid carcinoma (DTC). The aim of this study is to evaluate the usefulness and prognostic value of serum thyroglobulin (Tg) and the iodide-131 whole body scan (WBS) in DTC recurrences as a whole and according to the type of recurrence (local recurrence or distant metastases). PATIENTS AND METHODS: Thirty-four patients with recurrent DTC recruited in our institution over 15 years, with a minimum 5 years of follow-up and without either distant metastases at time of diagnosis nor detectable anti-Tg antibodies were included in the study. All patients were submitted to total or near-total thyroidectomy and 131INa ablation of postsurgical thyroid remnants. The follow-up included Tg measurement and WBS performed in hypothyroid state. RESULTS: Serum Tg was increased in the 67.4% of the patients and the WBS was positive in the 82.3%. In the isolated local recurrences the sensitivity of WBS was higher than Tg measurement (93.7 vs 43.7%; p < 0.05), but patients with positive Tg had a worse prognostic. By contrast, in patients with distant metastases the sensitivity of Tg was higher than WBS (83.3 vs 58.3%; p = NS). In 14 patients (41.2%) the results of WBS and Tg were in disagreement. In these cases a worse prognosis was observed when Tg was positive and WBS negative. CONCLUSIONS: The sensitivity of Tg and WBS is different depending on the type of recurrence. Therefore, both tests complement each other and it is not recommended to omit one of them in the follow-up of DTC.

Rendimiento diagnóstico de la determinación plasmática de tiroglobulina y del rastreo corporal con 131INA según el tipo de recurrencia en el carcinoma diferenciado de tiroides / Diagnostic performance of serum thyroglobulin and iodide-131Na scan according to the type of recurrence in differentiated thyroid carcinoma

Fundamento: No existe un consenso claro sobre cuál es el mejor protocolo de seguimiento en el carcinoma diferenciado de tiroides (CDT). El objetivo del estudio es analizar la utilidad y el significado pronóstico de la determinación plasmática de tiroglobulina (Tg) y el rastreo corporal con 131INa (RCT) en las recidivas de CDT tanto de forma global como según el tipo de recurrencia (recidiva local o metástasis a distancia). Pacientes y métodos: Se incluyen 34 pacientes con recurrencia de CDT recogidos durante un período de 15 años y con un seguimiento mínimo de 5 años, con anticuerpos antitiroglobulina negativos y sin metástasis en el momento del diagnóstico. En todos los casos se practicó la tiroidectomía total o casi total y ablación de restos con 131INa. El seguimiento posterior incluyó la determinación plasmática de Tg y el RCT realizados en situación de hipotiroidismo. Resultados: La Tg estaba elevada en el 64,7 por ciento de los pacientes y el RCT en el 82,3 por ciento. En la recidiva local aislada la sensibilidad del RCT fue superior a la de la Tg (93,7 frente a 43,7 por ciento; p < 0,05), pero los pacientes con Tg positiva tuvieron peor pronóstico. Por el contrario, en los pacientes con metástasis a distancia la sensibilidad de la Tg fue superior a la del RCT (83,3 frente a 58,3 por ciento; p = NS). En 14 pacientes (41,2 por ciento) el RCT y la Tg fueron discordantes. En estos casos observamos peor pronóstico cuando la Tg era positiva y el RCT negativo. Conclusiones: La sensibilidad de la Tg y el RCT es diferente según el tipo de recurrencia del CDT. Por tanto, ambas pruebas son complementarias y no puede prescindirse de ninguna de ellas en el seguimiento del CDT. (AU)

Short-term hypothyroidism has no effect on serum leptin concentrations.

The aim of the study is to determine the effect of short-term hypothyroidism on serum leptin levels. For this purpose 30 patients with past medical history of thyroidectomy for differentiated thyroid carcinoma were included. Serum leptin concentrations were similar when patients were on thyrotrophin-suppressive thyroxine therapy than when were admitted 4 weeks after stopping thyroxine treatment to perform a routine 131I scan in hypothyroid status (17.0 +/- s.e.m. 2.14 vs. 17.6 +/- s.e.m. 2.41 ng/ml; p = n.s.). Moreover, no differences were obtained when the analysis was performed separately in men and in women. We conclude that short-term hypothyroidism does not alter serum leptin concentrations. Furthermore, our results suggest that thyroid hormones do not operate through changes in serum leptin levels to regulate energy expenditure.

FISH analysis of 1cen-1q12 breakage, chromosome 1 numerical abnormalities and centromeric content of micronuclei in buccal cells from thyroid cancer and hyperthyroidism patients treated with radioactive iodine.

One of the health consequences of the Chernobyl nuclear power plant accident was a radioactive iodine-related increase in the incidence of thyroid cancer in exposed children. This radioisotope is used in the treatment of thyroid cancer and hyperthyroidism patients providing a convenient opportunity to study cytogenetic damage induced by known doses of radioactive iodine in treated patients. We used pancentromeric FISH on micronuclei and chromosome 1 tandem labelling FISH to monitor overall chromosome breakage and loss, 1q12 breakage and decondensation and chromosome 1 numerical abnormalities in buccal cells from 31 radioactive iodine-exposed hyperthyroidism and thyroid cancer patients. The overall outcome of the study, with 250,000 buccal cells analysed, is that there was no radioactive iodine-related increase in the frequency of micronuclei, 1q12 breakage, 1q12 decondensation or chromosome 1 numerical abnormalities. In addition, neither age nor gender, health status nor radioactive iodine dose modulated the frequency of the above cytogenetic end points. Although several uncertainties of these emerging molecular cytogenetic methodologies will require further experimentation, we conclude that, at the reported exposure levels, radioactive iodine did not induce detectable chromosome damage in buccal cells from treated patients.

Low sensitivity of the sister chromatid exchange assay to detect the genotoxic effects of radioiodine therapy.

To assess the genotoxic risk associated with 131I therapy, sister chromatid exchanges (SCEs) and cells with unusually high SCE counts (HFC) were determined in a follow-up study performed with 46 hyperthyroidism and 39 thyroid cancer patients treated with 131I. In addition, a cross-sectional study was also carried out with 78 control persons and 51 thyroid cancer patients that had completed radioiodine therapy from 1 to 6 years prior to the current investigation. In the follow-up analysis, the study was conducted over time and four blood samples were drawn from each patient: the first one prior to the radioiodine treatment, with the remaining three taken sequentially over the year after therapy. Concerning the results obtained for the whole population in the follow-up study, the SCE and HFC values found after radioiodine therapy did not show any significant increase, neither in the hyperthyroidism nor thyroid cancer groups. Unlike the results mentioned above, when the effect of smoking habit was considered, there was a slight but significant increase in SCE in the samples taken 3 months and 1 week after 131I therapy in the hyperthyroidism and thyroid cancer non-smokers, respectively. The data obtained in the cross-sectional study did not show differences in SCE and HFC between the control group and the cancer group treated with 131I. It is noteworthy that among the different parameters analysed, smoking habit is the only factor that showed a direct relationship with SCE and HFC and, as a consequence, smokers had significantly more SCE and HFC than non-smokers. Taking into account our previous investigations showing a highly significant increase in the frequency of micronuclei for the same patients and sampling times, the outcomes obtained would suggest that the eventual genotoxic effect of 131I therapy could not be clearly detected by the SCE assay. This would reinforce the view that ionizing radiation appears to be a poor inducer of SCEs.

Cytogenetic damage after 131-iodine treatment for hyperthyroidism and thyroid cancer. A study using the micronucleus test.

To detect the incidence and persistence of potential chromosome damage induced by iodine-131 therapy, we applied the cytokinesis-block micronucleus assay to peripheral blood lymphocytes from hyperthyroidism and thyroid cancer patients treated with 131I. Two groups of patients were evaluated in a longitudinal study; one group was composed of 47 hyperthyroid patients and the other of 39 thyroid cancer patients. In the hyperthyroidism group, the micronuclei frequency was determined before 131I therapy and 1 week, 1 month and 3 months after it. Furthermore, an additional sample was taken from a subgroup of 17 hyperthyroidism patients 6 months after treatment. In the thyroid cancer group, the analysis was also conducted over time, and four samples were studied: before treatment and 1 week, 6 months and 1 year later. Simultaneously, a cross-sectional study was performed with 70 control subjects and 54 thyroid cancer patients who had received the last therapeutic dose 1-6 years before the present study. In the hyperthyroidism group a significant increase in the micronuclei average was found over time. In the sample obtained 6 months after therapy, the micronuclei mean frequency was practically the same as in the sample taken 3 months before. In the thyroid cancer group a twofold increase in the frequency of micronuclei was seen 1 week after therapy. Although this value decreased across time, the micronuclei frequency obtained 1 year after 131I therapy remained higher than the value found before it. Concerning the data from the cross-sectional study, a significant increase in the frequency of micronuclei was detected in the subgroup of thyroid cancer patients treated between 1 and 3 years before the current study. These results indicate that exposure to 131I therapy induces chromosome damage in peripheral lymphocytes and that the cytokinesis-block micronucleus assay is sensitive enough to detect the genetic damage by exposure to sufficiently high levels of radiation from internal radioactive sources.

The alkaline single-cell gel electrophoresis (SCGE) assay applied to the analysis of radiation-induced DNA damage in thyroid cancer patients treated with 131I.

The alkaline single-cell gel electrophoresis (SCGE or Comet) assay appears to be a promising tool for measuring DNA damage at the individual cell level in both in vitro and in vivo studies. To provide further data on the possible applicability of this assay in human biomonitoring studies, we have evaluated the eventual genetic damage induced by therapeutic exposure to 131I, by measuring the Comet length and the amount of DNA damage in peripheral blood leukocytes from a group of 28 thyroid cancer patients who received 131I sodium iodide via oral administration. Blood samples were taken just before the treatment and 1 week after it. From the results obtained after radioiodine therapy, a small increase in the Comet length and in the grade of DNA damage is observed; however, this increase is not statistically significant because of inter-individual variability and the variable responses before and after 131I treatment. Considering our previous studies showing significant increases in the frequency of cytogenetic damage (when measured as micronuclei) in patients treated with relatively low doses of 131I, the results obtained in the present work by using the Comet assay could indicate that 1 week after the exposure most of the radioiodine-induced DNA lesions, that can be detected with this assay, have already been repaired.

Application of the single cell gel electrophoresis (SCGE) assay to the detection of DNA damage induced by 131I treatment in hyperthyroidism patients.

To provide further data on the possible applications of the single cell gel electrophoresis (SCGE) or Comet assay in human biomonitoring studies, we have evaluated the eventual genetic damage induced by therapeutic exposure to 131I, by measuring the tail length of the comet and the amount of DNA damage in peripheral blood cells from 16 hyperthyroidism patients treated with [131I]sodium iodide by oral administration. Blood samples were taken just before the treatment and 1 week and 1 month after. The results show a slight but significant increase in the mean tail length in the sample obtained 1 month after treatment. When the cells were classified according to the grade of damage the two post-treatment samples showed a clear increase in the proportion of damaged cells. The results of this study indicate that the DNA damage caused by 131I can be detected with the Comet assay, but when comparing the data reported here with our previous results obtained from the same patients and sampling times with the sensitive and well-established micronucleus test, the response in the Comet assay was less clear.