Radioactive iodine therapy leaves measurable DNA damage in thyroid cancer patients

Patients with thyroid cancer who receive radioactive iodine therapy show a sharp, measurable rise in chromosomal damage in their blood cells, and that damage had still not returned to baseline levels six months after treatment, according to a prospective study conducted at Charlotte Maxeke Johannesburg Academic Hospital in South Africa. The research, published in EJNMMI Reports, is described by its authors as the first study of its kind in a Sub-Saharan African population, and it adds longitudinal cytogenetic data to a body of international evidence linking iodine-131 therapy to DNA damage in treated patients.

The study enrolled 90 participants in total: 34 patients with thyroid cancer who were scheduled for radioactive iodine therapy, 26 patients with hyperthyroidism, and 30 healthy controls. Blood samples from the thyroid cancer patients were collected at four time points: on admission for radiotherapy, at discharge either three or five days after treatment depending on the administered activity, and again at three and six months after treatment. The comparison groups were sampled at baseline, providing a standard of reference against which the cancer patients’ pre-treatment chromosomal radiosensitivity could be assessed.

To quantify DNA damage, the researchers used the cytokinesis-block micronucleus assay, a well-established cytogenetic technique. Peripheral blood lymphocytes were stimulated to divide, and cytochalasin B was added to prevent the daughter cells from separating, producing binucleated cells that could be scored for micronuclei. Micronuclei are small structures in the cell cytoplasm formed from chromosome fragments or whole chromosomes that fail to be incorporated into the daughter nuclei during cell division. They are widely recognized as early biomarkers of chromosomal instability and unrepaired or misrepaired DNA damage. At least 1000 binucleated cells per condition were analysed for each patient, with all cultures performed in duplicate and scored under a fluorescent microscope.

The results showed a clear relationship between the amount of radioactive iodine administered and the level of induced chromosomal damage. The median activity of iodine-131 given to the thyroid cancer participants was 5550 megabecquerels, or 150 millicuries, with an interquartile range of 3700 to 7400 megabecquerels, corresponding to the range of 100 to 200 millicuries. The number of therapy-induced micronuclei increased with the amount of radioactive iodine activity administered, indicating an activity-dependent effect on genomic damage in the circulating lymphocytes.

The temporal pattern of damage was equally striking. The mean number of micronuclei per 1000 binucleated cells rose from 25.31 at admission, before any treatment, to 52.04 at discharge, a difference the authors describe as highly significant, with a p-value below 0.0001. The frequency then declined gradually, but remained elevated: at three months the mean stood at 46.47, and at six months it had fallen to 30.89, a statistically significant decrease between those two later time points with a p-value of 0.0385. Crucially, the six-month value still exceeded the pre-treatment baseline of 25.31, suggesting persistent genomic instability in these patients within the follow-up window.

This persistence matters because the general expectation, based on earlier research, is that micronucleus frequency typically peaks after exposure to DNA-damaging agents and then declines as cells repair the damage, with recovery to normal levels generally expected within a week to three months after therapy, depending on the severity of the damage and the individual’s repair capacity. The authors note that the persistence or delayed resolution of micronuclei may indicate ongoing genomic instability or impaired DNA repair processes, phenomena commonly observed in cancer and other diseases associated with chromosomal abnormalities. They also caution that the micronucleus assay, while a sensitive biomarker of chromosome damage and genomic instability, does not identify specific chromosomes or distinguish stable from unstable aberrations, so it should be interpreted as a global rather than a locus-specific measure of genotoxicity.

The study also examined whether age influenced the extent of therapy-induced DNA damage. Median micronucleus frequencies appeared slightly higher in participants under 40 years of age, but the distributions overlapped substantially and no statistically significant difference was observed between age categories, with a p-value of 0.2299. The authors conclude that within their relatively small cohort, radioiodine activity and underlying thyroid pathology appear to be more important drivers of micronucleus formation than chronological age alone. Baseline comparisons between the three groups revealed that the hyperthyroid group had the highest number of spontaneous micronuclei, with a mean of 33.95, compared with 25.31 in the thyroid cancer group and 23.23 in the controls, a pattern the authors note is consistent with previous studies of cytogenetic damage in patients treated with iodine-131 for hyperthyroidism and thyroid cancer.

The demographic profile of the cohort reflected the epidemiology of thyroid disease. Women made up 79 percent of all participants and 88 percent of the thyroid cancer group, in line with the known higher prevalence of thyroid disorders in women. Black participants constituted the majority across all three groups, a pattern the authors attribute partly to the country’s population distribution and to disparities in healthcare access, since the study was conducted in a public hospital setting. The thyroid cancer variant was documented for only 15 of the 34 patients, of whom six had the follicular variant and nine the papillary variant, with the remainder lacking recorded variant information. A substantial proportion of the thyroid cancer patients, 54 percent, presented with co-existing chronic illnesses such as HIV and hypertension.

The clinical context of these findings is significant. Radioactive iodine therapy is a standard component of thyroid cancer treatment, alongside thyroidectomy and hormone-suppressive therapy, and treatment guidelines vary from low activities of approximately 1110 megabecquerels to high activities ranging from 2960 to 11100 megabecquerels. However, secondary cancers have been reported in patients treated with radioactive iodine, including breast, colorectal, bone, prostate, pancreatic and kidney cancers, non-Hodgkin’s lymphoma and leukaemia. Acute radiation effects often present as hematologic malignancies, while chronic effects are indicated by the development of solid tumours. Higher activities of radioactivity can contribute to chromosomal aberrations and increase the predisposition to secondary cancers, and among female thyroid cancer patients treated with radioactive iodine, breast cancer is the most common secondary solid tumour in overall epidemiologic patterns, a point the authors clarify refers to population-level patterns rather than malignancies exclusively caused by radioiodine exposure.

The authors emphasize that their results underline the need for ongoing monitoring of chromosomal damage in thyroid cancer patients to understand the long-term implications of radioactive iodine therapy. They call for larger additional studies, the use of fluorescence in situ hybridization techniques to detect stable chromosomal aberrations, and longitudinal research with longer follow-up intervals, including investigation of patients who receive multiple consecutive radioiodine treatments, which they note is common in their clinical setting where patients often present with a high burden of disease. Such research, they anticipate, may elucidate the true impact of this routinely used treatment on DNA damage and genetic stability, and help identify individuals at higher risk of treatment-related complications.

Subject of Research: DNA damage measured in South African thyroid cancer patients treated with radioactive iodine

Article Title: DNA damage in thyroid cancer patients treated with radioactive iodine in Johannesburg, South Africa

Article References: Kagodora, S. B., Baeyens, A., Vral, A., & Di Tamba Willy Vangu, M. (2026). DNA damage in thyroid cancer patients treated with radioactive iodine in Johannesburg, South Africa. EJNMMI Reports, 10(1), Article 42. https://doi.org/10.1186/s41824-026-00327-2

Image Credits: AI Generated

DOI: 10.1186/s41824-026-00327-2

Keywords: thyroid cancer, radioactive iodine, iodine-131, DNA damage, micronucleus assay, chromosomal damage, genomic instability, secondary cancers, South Africa, radiation therapy, cytogenetics, prospective study