Mutagenesis, Vol. 14, No. 2, 221-226,
March 1999
© 1999 UK Environmental Mutagen Society/Oxford University Press
Low sensitivity of the sister chromatid exchange assay to detect the genotoxic effects of radioiodine therapy
1 Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Edifici Cn, Universitat Autònoma de Barcelona, 08193 Bellaterra and 2 Servei de Medicina Nuclear, Ciutat Sanitària i Universitària Vall d'Hebron, Pg. Vall d'Hebron 119, 08035 Barcelona, Spain
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and methodsResultsDiscussionReferences |
|---|
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.
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
Sister chromatid exchanges (SCEs) reflect the reciprocal interchange of DNA replication products at apparently homologous loci, which involves DNA breakage and reunion (Latt et al., 1981
). Since the development of the 5-bromodeoxyuridine (BrdU) staining technique for the morphological differentiation of sister chromatids (Perry and Wolf, 1974), many works have been published about SCE induction after in vivo and in vitro exposure to genotoxic agents (Tucker et al., 1993; Tucker and Preston, 1996). Such studies have demonstrated that a great number of mutagens increase the SCE frequency at concentrations which are far lower than those required to produce chromosome aberrations. Besides the advantages of SCE as a sensitive indicator of genotoxicity, the use of SCE as a cytogenetic end-point has been the subject of criticism because, to date, the molecular mechanisms of SCE formation and its biological meaning are not completely understood (Li and Loretz, 1991; Tucker and Preston, 1996). However, for many authors, the analysis of SCE has been considered to be highly sensitive for measuring the mutagenic and carcinogenic potential of many environmental agents (Tucker et al., 1993).
Although ionizing radiations are well-known DNA damaging agents (Meltz, 1991; Ward, 1995), it was observed early that radiation is a poor inducer of SCEs (Perry and Evans, 1975). The extent of stimulation of SCE by in vitro irradiation varies from no increase to levels as high as 2- to 3-fold the basal level (Perry and Evans, 1975; Littlefield et al., 1979; Morgan and Crossen 1980; Gundy et al., 1984; Nagasawa et al., 1990; Ribas et al., 1994). On the other hand, different investigations have shown that in vivo and in vitro ionizing radiation exposure is capable of inducing SCEs in cells radiosensitized by BrdU incorporation into DNA (Abramovsky et al., 1978; Renault et al., 1982; Morales-Ramírez et al., 1984, 1998). Nevertheless, the question of SCE induction in cells irradiated without BrdU incorporation is less clear (Gundy et al., 1984). With regard to the application of the SCE assay for the biomonitoring of human populations exposed to ionizing radiation, there is some data indicating no increases in the SCE level (Brandom et al., 1990; Yang et al., 1997), although other authors have shown significant increases in the frequency of SCEs in cultured lymphocytes from persons occupationally, accidentally or therapeutically exposed to ionizing radiation (Gundy et al., 1984; Al-Sabti et al., 1992; Lazutka and Dedonyté, 1995; Sönmez et al., 1997). Thus, the results reported up to now on SCE induction after in vivo ionizing radiation exposure in human populations are rather contradictory.
The diagnostic and therapeutic use of 131I for the treatment of hyperthyroidism (Graves's disease and non-toxic multinodular goitre) and thyroid cancer (papillary and folicullar thyroid carcinoma) have been routine for decades (Farrar and Toft, 1991; Huysmans et al., 1997; Mazzaferri, 1997). In recent years, the therapeutic use of 131I in hyperthyroidism and cancer thyroid patients has been assessed for genetic risk in order to evaluate its eventual hazard (Dottorini, 1996). In this context, several investigations focused on the evaluation of the genotoxic effects of 131I therapy have demonstrated significant increases in the frequency of chromosome aberrations (Baugnet-Mahieu et al., 1994; Gundy et al., 1996; M'Kacher et al., 1996) and micronuclei (Catena et al., 1994; Wuttke et al., 1996; Gutiérrez et al., 1997; Ramírez et al., 1997) in peripheral blood lymphocytes from patients with hyperthyroidism and thyroid cancer after 131I treatment.
To add new data on the applicability of the SCE assay in the biomonitoring of human populations exposed to ionizing radiation, and following our previous investigations on the potential genotoxic effects of 131I therapeutic exposure, we have monitored hyperthyroidism and thyroid cancer patients treated with radioiodine in a follow-up and a cross-sectional study, by analysing the frequency of SCE and the percentage of cells with unusually high SCE counts, termed high frequency cells (HFC), in cultured human lymphocytes.
|
Materials and methods |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
Follow-up study
A follow-up or longitudinal study was carried out in two different groups. One group consisted of 46 hyperthyroidism patients (38 women and eight men) and the other consisted of 39 thyroid cancer patients (27 women and 12 men). All these patients were treated at the Nuclear Medicine Service of the University Hospital of Vall d'Hebron (Barcelona). The hyperthyroidism patients received Na131I (148–1287 MBq) by oral administration as treatment. Four blood samples were taken from all patients of this group: before the radioiodine therapy and 1 week, 1 month and 3 months after.
In contrast to the hyperthyroidism patients, the thyroid cancer patients, after a nearly total thyroidectomy, received Na131I as an ablative treatment. They were treated with higher activities (3700–5550 MBq) than those administered to the hyperthyroidism patients and four blood samples were obtained: the first before therapy and the following were taken 1 week, 6 months and 1 year after.
This study design, with repeated measures over time, allows each subject sampled before exposure to act as his/her own control.
All individuals gave informed consent and blood samples were collected and further manipulated in accordance with ethical standards. Demographic characteristics as well as medical and occupational histories were documented by questionnaires that included questions on variables known to influence SCE expression, such as cigarette smoking.
Cross-sectional study
Simultaneously with the longitudinal study, a cross-sectional study was also conducted. It was carried out with a group of 78 control subjects and a group of 51 patients that had developed thyroid cancer in the previous years and, consequently, were treated with 131I. The control group constituted healthy persons (33 women and 45 men) working at the Bellaterra University Campus (Barcelona), without indication of previous occupational or accidental exposure to radioactive sources or other agents suspected of genotoxicity.
The patient group (41 women and 10 men) presented with follicular or papillary thyroid cancer and all of them received Na131I orally as an adjuvant treatment for any residual tumour cells after thyroidectomy. The total dose administered (2220–37518 MBq) results from adding the various 131I therapeutic doses (in some cases repeated doses were administered to treat local recurrence of malignant disease) plus an annual dose of ~185 MBq administered to detect active tissue. The patients were selected on the basis that they were administered with their last therapeutic dose between 1 and 6 years before the current study. Blood samples were obtained 1 year after the last annual check-up dose.
As in the follow-up study, the standard demographic questions, as well as occupational, medical and family history, were determined. The blood samples were also collected and further manipulated following ethical standards.
Lymphocyte cultures
Blood was obtained using heparinized vacutainer tubes. Prior to culture, 5 ml of whole blood were centrifuged and the supernatant removed to eliminate blood plasma and hence to homogenize the cultures. The original blood volume was reconstituted by adding culture medium RPMI 1640. Two replicates from each individual were made. The cultures were established and harvested as described elsewhere (Carbonell et al., 1995; Pitarque et al., 1997). Air dried preparations were made and the slides were then stained by the fluorescence plus Giemsa procedure (Perry and Wolf, 1974). We purchased Giemsa from Merck (Darmstadt, Germany), BrdU and Hoechst 33258 dye from Eastman Kodak (New York, NY) and all other chemicals were obtained from Gibco (Eragny, France)
SCE analysis
To determine the SCE mean frequency per cell for each subject, a total of 50 well-spread metaphases (25 per replicate) containing 46 ± 1 chromosomes were examined on coded slides. The percentage of high frequency cells (%HFC) for each individual was estimated using the pooled distribution of all SCE measurements. We defined HFC as those cells that display >95th percentile of the distribution of SCE per cell in the population. A total of 100 metaphases was examined to determine the proportion of cells that undergo one, two or more divisions and to calculate the proliferation rate index (PRI) according to Lamberti et al. (1983).
Statistical analysis
The data were analysed using the CSS:STATISTICA/W(TM) (StatSoft, Tulsa, OK) statistical package. The distribution of the mean SCE frequencies and %HFC were compared with the normal distribution by means of the Kolmogorov–Smirnov test of goodness of fit. The distribution of the SCE means did not depart significantly from normality, therefore parametric tests were adequate for statistical analysis of the SCE data. In contrast, a significant departure from normality was shown by the HFC 95th, therefore, non-parametric tests were chosen for statistical analysis of the HFC values.
When the different post-radioiodine treatment data were compared with the pre-treatment values in the follow-up study, the t-test for dependent samples and the Wilcoxon matched pairs test were used for SCE means and %HFC, respectively. In the cross-sectional study, to compare the two parameters studied between the control and patient groups, the t-test for independent samples and the Mann-Whitney U-test were used.
The possible effects that the different activities of 131I administered, the demographic factors and the lifestyle factors could have on SCE and HFC were evaluated using a multiple regression analysis, in both the follow-up and the cross-sectional studies.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
Follow-up study
Two groups of patients therapeutically exposed to 131I were evaluated in a follow-up study: a group of 46 hyperthyroidism patients monitored for 3 months and a group of 39 thyroid cancer patients monitored for 1 year.
Table I summarizes the characteristics of the group of hyperthyroidism patients where the smoking status and the average dose administered and age are indicated, together with the mean values of SCE, HFC and PRI obtained in the four sampling periods. These patients received, as treatment, a mean activity (± SE) of 131I of 550.82 ± 44.67 MBq, the mean age of the group being 48.04 ± 2.90 years. When considering the pooled data, it appears that the SCE and HFC values obtained after the 131I treatment are not different from those obtained before it. Moreover, in the three post-treatment samples evaluated, neither the SCE mean nor %HFC show a significant relationship with the dose administered to the patients. In this point it is interesting to point out that a fifth sample was also taken 6 months after treatment, but from only 17 subjects, and the SCE average had not changed over time. Thus, in this small subgroup, the SCE means (± SE) obtained after treatment were similar to those found before it: 7.50 ± 0.24; 7.57 ± 0.25; 7.71 ± 0.22; 7.64 ± 0.22; 7.71 ± 0.33 (data not shown in Table I).
|
The PRI average, reflecting the proliferative activity of the lymphocytes, did not seem to be affected by the 131I treatment in either of the groups studied, the values obtained being similar to those previously found in other populations following the same experimental procedures (Carbonell et al., 1995
; Pitarque et al., 1997).
When the influences of age and lifestyle on SCE and HFC were analysed, only smoking habit showed a significant direct relationship with both parameters. Therefore, in order to determine the eventual effect of radioiodine therapy on the SCE mean and the HFC percentage for each smoking group, the patients were classified as non-smokers, ex-smokers and smokers. The summary data, as well as the values obtained in the three subgroups are also indicated in Table I
. When comparing the SCE frequency obtained before radioiodine therapy with those obtained after it, no statistically significant differences were found, except for the SCE mean in the sample taken 3 months after therapy, where it reaches a significant increase for non-smokers. With reference to %HFC obtained in the different subgroups, no differences were observed in the samples taken after 131I treatment. Furthermore, the activities administered to each smoking group did not show a significant relationship with SCE or HFC values.
Table I also indicates that the SCE frequencies and %HFC in smokers were significantly higher than in non-smokers, both before the therapy and in the samples taken 1 week and 1 month later.
Table II shows the data obtained in the follow-up study with the thyroid cancer patients. This table indicates the smoking status and the average dose administered and age, together with the SCE, %HFC and PRI values obtained in the four sampling periods studied. These patients received, as ablative treatment, a mean activity of 4070 ± 63.75 MBq of 131I and the mean age of the group was 42.64 ± 2.81 years. When considering the pooled data, a small increase in the SCEs mean was observed 1 week after radioiodine therapy, although this increase did no attain statistical significance. On the other hand, in the sample taken 1 year after therapy, a reduction in the SCEs mean was observed, this reduction being statistically significant. When the percentage of HFC was analysed, no differences over time were observed.
|
The statistical analysis on the influence of the administered 131I activity, age and lifestyle on SCE and HFC revealed that only smoking habit shows a significant positive relationship with both parameters. Thus, Table II
gives the SCE, %HFC and PRI mean values corresponding to non-smokers, ex-smokers and smokers, as well as for the overall group of thyroid cancer patients. As indicated, only a slight but significant increase in the SCE mean for the sample obtained 1 week after 131I treatment in the non-smoker group was observed. Regarding the significant reduction observed 1 year after 131I in the whole group, a weak reduction was also observed for each smoking group, but it did not attain statistical significance. In addition, when the effect of smoking habit is considered, the statistical analysis indicates that for all the sampling times both the SCE mean and %HFC are higher in the smoker group. It must be pointed out that due to the low number of ex-smokers, they were not included in the evaluation of the 131I effects when smoking habit was considered.
Cross-sectional study
Simultaneously with the follow-up study, an extended investigation with a group of 51 patients who presented with thyroid cancer and were treated with 131I 1–6 years before the current study was also undertaken. These data were compared with a concurrent matched control group of 78 healthy donors.
The main features of the control and exposed groups, as well as the results corresponding to the SCE assay, are presented in Table III. No statistically significant differences in the SCE mean or %HFC were observed between the control and the thyroid cancer group. As in the follow-up study, the PRI average is not influenced by 131I treatment.
|
Taking into account that the half-life of lymphocytes in the peripheral blood stream is ~3 years (Evans, 1986
), the thyroid cancer patients were classified in two groups: a first group, who received the last treatment dose within 12–36 months previous to the cytogenetic analysis, and a second group, who received the last treatment within 37–72 months prior to the present study. When comparing the values obtained in the two groups of treated patients with those obtained in the control group, no statistically significant differences were found (Table III).
With regard to the different parameters analysed, only smoking habit shows a direct relation with the SCE and %HFC means. Thus, Table IV summarizes the results for cancer patients and controls when smoking status is considered. Although no differences between the two groups are observed, the SCE and HFC data are statistically higher in smokers than in non-smokers for the exposed patients, as well as for the total of individuals studied. On this point, it must be recalled that the ex-smokers were not included in the analysis. Finally, neither the non-smoker nor the smoker groups showed any significant relationship between the administered total dose and SCE or HFC.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
Although SCE induction has proved to be a useful and sensitive indicator of genotoxic exposure, a conflicting question is whether the level of SCE is or is not affected by ionizing radiation? Thus, there are contradictory results both in human lymphocytes exposed to radiation in vitro and in biomonitoring studies of human populations exposed to ionizing radiation. In this context, our results obtained by means of follow-up and cross-sectional analyses of patients treated with 131I seem to confirm that ionizing radiation is a poor inducer of SCE, since neither SCE nor HFC show a clear increase after radioidine therapy.
Our data are in agreement with previous studies where no significant increases in SCE frequency in lymphocytes were detected, neither from plutonium workers with cumulative chronic external irradiation (Brandom, et al., 1990) nor from a patient accidentally exposed to a 192Ir source (Littlefield, 1982). Moreover, a recent report on biodosimetry from astronauts exposed to ionizing radiation in space has not revealed differences between the SCE frequency found before and after a Mir-18 flight (Yang et al., 1997). Nevertheless, our data are in constrast to the results previously reported by Gundy et al. (1984), Al-Sabti et al. (1992) and Lazutka and Dedonyté (1995), who obtained significant SCE increases in different populations occupationally or accidentally exposed to ionizing radiation.
In spite of the reservations expressed, it is noteworthy that in the samples taken 1 week and 3 months after 131I treatment, a slight but significant increase in the SCE frequency was observed for non-smokers in the follow-up study. Sönmez et al. (1997) also reported a significant SCE increment in a non-smoker group 72 h after exposure to low doses of 131I (370 kBq) for thyroid scintigraphy.
Previous studies carried out by us in the same patients and for the same sampling periods showed a clear induction of genetic damage as a consequence of 131I exposure, when the induction of micronuclei in binucleated (BNMN) cells was used as a genetic end-point. Therefore, the negative results obtained in this study are not due to a lack of genotoxic effect of 131I exposure. Thus, in the hyperthyroidism group, the increase in BNMN persisted for at least 3 months after 131I treatment (Gutiérrez et al., 1997), while in the thyroid cancer group, a clear 2-fold increase in the BNMN frequency was found 1 week after therapy (Marcos et al., 1997). In relation to the cross-sectional study, the lack of differences between controls and cancer patients for SCEs and %HFC is apparently not in agreement with the significant increase in BNMN observed in the group sampled 1–3 years after radioiodine therapy (Marcos et al., 1997). As indicated above, our results show that the SCE assay seems to be less sensitive than the MN test in demonstrating radioiodine-induced DNA lesions; this would obviously reflect the fact that each end-point measures a different type of genetic damage. Moreover, it must be recalled that unlike BNMN evaluation, SCE analysis is carried out in metaphases of the second division and, consequently, cells with radiation-induced structural chromosome aberrations may be eliminated during the first division in culture (Boei et al., 1996). Therefore, the frequency of SCE per cell might be distorted due to the elimination of cells with high SCE yields.
Up to now, few explanations for the insensitivity of the SCE assay in detecting radiation damage have been found in the literature. This could be due, at least partially, to the fact that the mechanisms and biological significance of SCE formation still remain to be completely elucidated. Ionizing radiation would be expected to be a weak inducer of SCE, because the resulting DNA damage would be repaired before DNA replication (Preston, 1991). Thus, it is generally accepted that radiations of low linear energy transfer (LET), such as X- or 
-rays, do not produce any increase in SCE in prestimulated lymphocytes (Littlefield et al., 1979; Morgan and Crossen, 1980). In contrast, high LET radiations, such as 
-particles, can induce SCE in human lymphocytes (Aghamohammadi et al., 1988; Schmid and Roos, 1996), due to the fact that some of the DNA lesions induced by high LET particles seem to have a longer life than those produced by X- or -rays and, therefore, would persist until DNA synthesis, leading to SCE induction (Schmid and Roos, 1996). Taking into account the above mentioned and that 131I is a ß- and -emitter, our data on the lack of SCE induction after the administration of 131I to treat hyperthyroidism and thyroid cancer could be explained by the relative rapidity of repair of the DNA lesions leading to the formation of SCEs.
On the other hand, and concerning the slight decrease in the SCE frequency observed 1 year after 131I therapy in the thyroid cancer patients from the follow-up study, it should be indicated that significant monthly variations in SCE data have been reported (Tucker et al., 1988). Taking this into account, we investigated whether the decrease found in our study could be due to this reason. Nevertheless, from our data there is not a significant correlation between SCE frequency and sampling time and, as a consequence, the seasonal variation cannot be a plausible explanation for our results.
As previously reported in several studies (Bender et al., 1988; Carrano and Natarajan, 1988), our results confirm once again that smoking has a significant influence on SCE and HFC frequencies. Thus, in both the follow-up and the cross-sectional studies, the SCE mean was statistically higher in smokers than in non-smokers at most of the sampling times. The fact that no other source of variation was found indicates that smoking is one of the most important confounding factors in the analysis of SCEs when conducting biomonitoring studies, therefore, smoking habit must be considered to avoid misleading results (Carrano and Natarajan, 1988).
In conclusion, our findings indicate that SCE analysis in hyperthyroidism and thyroid cancer patients does not reflect the eventual genotoxic effects of 131I therapy, which would reinforce the view that ionizing radiation is a poor SCE inducer.
|
Acknowledgments |
|---|
We would like to thank T.Amador, A.Corral and G.Umbert for their expert technical help in the preparation and scoring of samples and M.McCarthy for her secretarial assistance. This investigation has been supported in part by the Spanish Ministry of Education and Culture (SAF95-0813, CICYT) and by the Generalitat de Catalunya (SGR95-00512, CIRIT).
|
Notes |
|---|
3 To whom correspondence should be addressed. Tel: +34 93 581 20 52; Fax: +34 93 581 23 87; Email: rmd{at}cc.uab.es
|
References |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
-
Abramovsky,I., Vorsanger,G. and Hirschorn,K. (1978) Sister chromatid exchange induced by X-rays of human lymphocytes and the effect of L-cysteine. Mutat. Res., 50, 93–100.[Web of Science][Medline]
Aghamohammadi,S.Z., Goodhead,D.T. and Savage,J.R.K. (1988) Induction of sister chromatid exchanges (SCE) in G0 lymphocytes by plutonium-238 -particles. Int. J. Radiat. Biol., 53, 909–915.
Al-Sabti,K., Lloyd,D.C., Edwards,A.A. and Stegnar,P. (1992) A survey of lymphocyte chromosomal damage in Slovenian workers exposed to occupational clastogens. Mutat. Res., 280, 215–223.[Web of Science][Medline]
Baugnet-Mahieu,L., Lemaire,M., Léonard,E.D., Léonard,A. and Gerber,G.B. (1994) Chromosome aberrations after treatment with radioactive iodine for thyroid cancer. Radiat. Res., 140, 429–431.[Web of Science][Medline]
Bender,M.A., Preston,R.J, Leonard,R.C., Pyatt,B.E., Gooch,P.C. and Shelby,M.D. (1988) Chromosomal aberration and sister-chromatid exchange frequencies in peripheral blood lymphocytes of a large human population sample. Mutat. Res., 204, 421–433.[Web of Science][Medline]
Boei,J.J.W.A., Vermeulen,S. and Natarajan,A.T. (1996) Detection of chromosomal aberrations by fluorescence in situ hybridization in the first three postirradiation divisions of human lymphocytes. Mutat. Res., 349, 127–135.[Web of Science][Medline]
Brandom,W.F., McGavran,L., Bistline,R.W. and Bloom,A.D. (1990) Sister chromatid exchanges and chromosome aberration frequencies in plutonium workers. Int. J. Radiat. Biol., 58, 195–207.[Web of Science][Medline]
Carbonell,E., Peris,F., Xamena,N., Creus,A. and Marcos,R. (1995) SCE analysis in human lymphocytes of a Spanish control population. Mutat. Res., 335, 35–46.[Web of Science][Medline]
Carrano,A.V. and Natarajan A.T. (1988) Considerations for population monitoring using cytogenetic techniques. Mutat. Res., 204, 379–406.[Web of Science][Medline]
Catena,C., Villani,P., Nastasi,R., Conti,D., Righi,E., Salerno,G., Righi,V.A. and Ronga,G. (1994) Micronuclei and 3AB-index in patients receiving iodine-131 therapy. J. Nucl. Biol. Med., 38, 586–593.
Dottorini,M.E. (1996) Genetic risk assessment after iodine-131 exposure: an opportunity and obligation for nuclear medicine. J. Nucl. Med., 37, 612–615.
Evans,H.J. (1986) What has been achieved with cytogenetic monitoring? In Sorsa,M. and Norppa,H. (eds), Monitoring of Occupational Genotoxicants. Alan R.Liss, New York, NY, pp. 3–23.
Farrar,J.J. and Toft,A.D. (1991) Iodine-131 treatment of hyperthyroidism: current issues. Clin. Endocrinol., 35, 207–212.[Medline]
Gundy,S., Varga,L. and Bender,M.A. (1984) Sister chromatid exchange frequency in human lymphocytes exposed to ionizing radiation in vivo and in vitro. Radiat. Res., 100, 47–54.[Web of Science][Medline]
Gundy,S., Katz,N., Füzy,M. and Ésik, O (1996) Cytogenetic study of radiation burden in thyroid disease patients treated with external irradiation or radioiodine. Mutat. Res., 360, 107–113.[Web of Science][Medline]
Gutiérrez,S., Carbonell,E., Galofré,P., Creus,A. and Marcos,R. (1997) Micronuclei induction by 131I exposure. Study in hyperthyroidism patients. Mutat. Res., 373, 39–45.[Web of Science][Medline]
Huysmans,D., Hermus,A., Edelbroek,M., Barentsz,J., Corstens,F. and Kloppenborg,P. (1997) Radioiodine for nontoxic multinodular goiter. Thyroid, 7, 235–239.[Web of Science][Medline]
Lamberti,L., Bigatti Ponzetto,P. and Ardito,G. (1983) Cell kinetics and sister-chromatid exchange frequency in human lymphocytes. Mutat. Res., 120, 193–199.[Web of Science][Medline]
Latt,S.A., Allen,J., Bloom,S.E., Carrano,A., Falke,E., Kram,D., Schneider,E., Schreck,R., Tice,R., Whitfield,B. and Wolff,S. (1981) Sister-chromatid exchanges: a report of the Gene-Tox Program. Mutat. Res., 87, 17–62.[Web of Science][Medline]
Lazutka,J.R. and Dedonyté,V. (1995) Increased frequency of sister chromatid exchanges in lymphocytes of Chernobyl clean-up workers. Int. J. Radiat. Biol., 67, 671–676.[Web of Science][Medline]
Li,A.P. and Loretz,L.J. (1991) Assays for genetic toxicity. In Li,A.P. and Heflich,R.H. (eds), Genetic Toxicology. CRC Press, Boca Raton, FL, pp. 119–141.
Littlefield,L.G. (1982) Effects of DNA-damaging agents on SCE. In Sandberg,A.A. (ed.), Sister Chromatid Exchange. Alan R.Liss, New York, NY, pp. 355–394.
Littlefield,L.G., Colyer,S.P., Joiner,E.E. and Dufrain,R.J. (1979) Sister chromatid exchanges in human lymphocytes exposed to ionizing radiation during G0. Radiat. Res., 78, 514–521.[Web of Science][Medline]
Marcos,R., Gutiérrez,S., Carbonell,E., Ramírez,M.J., Galofré,P. and Creus,A. (1997) Cytogenetic follow-up study on hyperthyroidism and thyroid cancer patients treated with 131I. Cytogenet. Cell, Genet., 77, 30.
Mazzaferri,E.L (1997) Thyroid remnant 131I ablation for papillary and follicular thyroid carcinoma. Thyroid, 7, 265–271.[Web of Science][Medline]
Meltz,M.L. (1991) Physical mutagens. In Li,A.P. and Heflich,R.H. (eds), Genetic Toxicology. CRC Press, Boca Raton, FL, pp. 203–256.
M'Kacher,R., Legal,J.D., Schlumberger,M., Voisin,P., Aubert,B., Gaillard,N. and Parmentier,C. (1996) Biological dosimetry in patients treated with iodine-131 for differentiated thyroid carcinoma. J. Nucl. Med., 37, 1860–1864.[Web of Science][Medline]
Morales-Ramírez,P., Vallarino-Kelly,T. and Rodríguez-Reyes,R. (1984) In vivo persistence of sister chromatid exchange (SCE) induced by gamma rays in mouse bone marrow cells. Environ. Mutagen., 6, 529–537.[Web of Science][Medline]
Morales-Ramírez,P., Mendiola-Cruz,M.T. and Cruz-Vallejo,V. (1998) Effect of vitamin C or ß-carotene on SCE induction by gamma rays in radiosensitized murine bone marrow cells in vivo. Mutagenesis, 13, 139–144.
Morgan,W.F. and Crossen,P.E. (1980) X irradiation and sister chromatid exchange in cultured human lymphocytes. Environ. Mutagen., 2, 149–155.[Web of Science][Medline]
Nagasawa,H., Little,J.B., Inkret,W.C., Carpenter,S., Thompson,K., Raju,M.R., Chen,D.J. and Strniste,G.F. (1990) Cytogenetic effects of extremely low doses of plutonium-238 alpha-particle irradiation in CHO K-1 cells. Mutat. Res., 244, 233–238.[Web of Science][Medline]
Perry,P. and Evans,H.J. (1975) Cytological detection of mutagen-carcinogen exposure by sister chromatid exchange. Nature, 258, 121–125.[Medline]
Perry,P. and Wolff,S. (1974) New Giemsa method for the differential staining of sister chromatids. Nature, 251, 156–158.[Medline]
Pitarque,M., Carbonell,E., Lapeña,N., Marsá,M., Valbuena,A., Creus,A. and Marcos,R. (1997) SCE analysis in peripheral blood lymphocytes of a group of filling station attendants. Mutat. Res., 390, 153–159.[Web of Science][Medline]
Preston,R.J. (1991) Mechanisms of induction of chromosomal alterations and sister chromatid exchanges: presentation of a generalized hypothesis. In Li,A.P. and Heflich,R.H. (eds), Genetic Toxicology. CRC Press, Boca Raton, FL, pp. 41–65.
Ramírez,M.J., Surrallés,J., Galofré,P., Creus,A. and Marcos,R. (1997) Radioactive iodine induces clastogenic and age-dependent aneugenic effects in lymphocytes of thyroid cancer patients as revealed by interphase FISH. Mutagenesis, 12, 449–455.
Renault,G., Gentil,A. and Chouroulinkov,I. (1982) Kinetics of induction of sister-chromatid exchanges by X-rays through two cell cycles. Mutat. Res., 94, 359–368.[Web of Science][Medline]
Ribas,G., Carbonell,E., Xamena,N., Creus,A. and Marcos,R. (1994) Genotoxicity of tritiated water in human lymphocytes. Toxicol. Lett., 70, 63–69.[Web of Science][Medline]
Schmid,E. and Roos,H. (1996) Dose dependence of sister chromatid exchanges in human lymphocytes induced by in vitro -particle irradiation. Radiat. Environ. Biophys., 35, 311–314.[Web of Science][Medline]
Sönmez S., Íkbal,M., Yíldírím,M., Gepdiremen,A. and Öztas,S. (1997) Sister chromatid exchange analysis in patients exposed to low dose of iodine-131 for thyroid scintigraphy. Mutat. Res., 393, 259–262.[Web of Science][Medline]
Tucker,J.D. and Preston,R.J. (1996) Chromosome aberrations, micronuclei, aneuploidy, sister chromatid exchanges and cancer risk assessment. Mutat. Res., 365, 147–159.[Web of Science][Medline]
Tucker,J.D., Ashworth,L.K., Johnston,G.R., Allen,N.A. and Carrano,A.V. (1988) Variation in the human lymphocyte sister-chromatid exchange frequency: results of a long-term longitudinal study. Mutat. Res., 204, 435–444.[Web of Science][Medline]
Tucker,J.D., Auletta,A., Cimino,M.C., Dearfield,K.L., Jacobson-Kram,D., Tice,R.R. and Carrano,A.V. (1993) Sister-chromatid exchange: second report of the Gene-Tox program. Mutat. Res., 297, 101–180.[Web of Science][Medline]
Ward,J.F. (1995) Radiation mutagenesis: the initial DNA lesions responsible. Radiat. Res., 142, 362–368.[Web of Science][Medline]
Wuttke,K., Streffer,C., Müller,W.-U., Reiners,C., Biko,J. and Demidchik,E. (1996) Micronuclei in lymphocytes of children from the vicinity of Chernobyl before and after 131I therapy for thyroid cancer. Int. J. Radiat. Biol., 69, 259–268.[Web of Science][Medline]
Yang,T.C., George,K., Johnson,A.S., Durante,M. and Fedorenko,B.S. (1997) Biodosimetry results from space flight Mir-18. Radiat. Res., 148, S17-S23.[Web of Science][Medline]
Received on July 17, 1998; accepted on September 25, 1998.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M.J. Ramirez, S. Puerto, P. Galofre, E.M. Parry, J.M. Parry, A. Creus, R. Marcos, and J. Surralles Multicolour FISH detection of radioactive iodine-induced 17cen-p53 chromosomal breakage in buccal cells from therapeutically exposed patients Carcinogenesis, August 1, 2000; 21(8): 1581 - 1586. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||