Baseline and treatment-induced chromosomal abnormalities in peripheral blood lymphocytes of Hodgkin's lymphoma patients.

PURPOSE: To study chromosomal abnormalities in 49 patients with Hodgkin's lymphoma (HL), before and after treatment and at several times during a 2-year period. METHODS AND MATERIALS: Simple chromosomal aberrations (CAs) and complex chromosomal rearrangements (CCRs) were counted in peripheral lymphocytes by painting of chromosomes 1, 3, and 4 (fluorescence in situ hybridization). A control population was composed of 20 healthy donors and 69 untreated cancer patients who had undergone various radiologic scans. RESULTS: A greater frequency (p < 10(-4)) of spontaneous cytogenetic abnormalities was observed in untreated HL patients compared with the control populations. CCRs were observed exclusively in the HL population (p < 10(-4)). Chemotherapy was associated with a significant increase in the frequency of CAs (p < 10(-4)), according to the chemotherapy regimen (p = 0.002). Immediately after radiotherapy, a significant increase (p < 10(-4)) was observed in CAs according to the size of the irradiation field. Conversely, the significant increases in the frequency of CCRs observed after treatment did not correlate with the chemotherapy regimens, radiotherapy dose, or size of the irradiation field. The evolution of CAs vs. CCRs over time was also dissociated: during the follow-up of these patients, a significant decrease was observed in the frequency of CAs at 6 months and 1 and 2 years. In contrast, after an initial decrease for up to 6 months after treatment, the frequency of CCRs remained constant for up to 2 years. CONCLUSION: Increased cytogenetic abnormalities were observed in untreated HL patients compared with the control populations. The greater frequency of cytogenetic abnormalities persisted in some patients. The presence of CCRs supports the concept of a unique genetic environment in HL patients that persists in response to potentially noxious treatments.

Premature chromosome condensation associated with fluorescence in situ hybridisation detects cytogenetic abnormalities after a CT scan: evaluaton of the low-dose effect.

The purpose of this study was to assess the cytogenetic effects of the X ray irradiation used during a CT scan in order to estimate the mean absorbed dose in circulating lymphocytes. Chromosomal aberrations were scored in blood lymphocytes of ten patients undergoing CT scans, by applying fluorescence in situ hybridisation (FISH) to metaphase cells and premature chromosome condensation (PCC) with chromosomes 1, 3 and 4 painting probes immediately after exposure. This generated a dosimetric index that reflects the dose to the circulating lymphocytes. By using PCC a significant increase in the frequency of chromosomal fragment was observed immediately after a CT scan. However, no significant increase in chromosomal aberration was detected in metaphase cells. The mean dosimetric index immediately after exposure was 0.057 Gy (95% CI: 0.052-0.082 Gy). This dosimetric index depends essentially on the size of the examined and exposed blood volumes. This dose is in close agreement with the dose length product (DLP) (Gy cm) (R = 0.80). It should be kept in mind when justifying requests for diagnostic CT scan especially in young patients. The presence of chromosomal fragments after a CT scan indicated the cytogenetic effect of a low dose. PCC associated with chromosome painting is a method for detecting the cytogenetic effect of a low dose immediately after exposure.

Radiosensitivity of human normal and tumoral thyroid cells using fluorescence in situ hybridization and clonogenic survival assay.

PURPOSE: By using cell survival as a reference, we evaluated the radiosensitivity of human normal and tumoral thyroid cells using of radiation-induced translocations. METHODS AND MATERIALS: Tissue samples were obtained from patients undergoing thyroidectomy. Cell cultures were established, irradiated with 60Co, and metaphases painted using commercial whole-chromosome 4 hybridization probe and pancentromeric probe. The clonogenic survival was assessed by conventional colony forming assay. RESULTS: After irradiation, normal cultured thyroid cells yielded a higher number of translocations than cultures derived from adenomas or thyroid carcinoma. The colony forming assay demonstrated, by way of the mean inactivation dose, a higher survival of thyroid carcinoma and adenoma cells than of normal thyroid cells. This difference between tumoral and nontumoral cells is significant in each method (p = 0.0001), and cannot be explained by apoptosis in irradiated malignant cells. Correlation of the results obtained by both methods is shown by comparing the survival fraction at 2 Gy (SF2) and the percentage of chromosome 4 translocations at 2 Gy. CONCLUSION: These results indicate that the yield of radiation-induced translocations serves as a good and rapid prediction of the intrinsic radiosensitivity of thyroid cells, and that this test could be applied to other tumors.

Biologic dosimetry in thyroid cancer patients after repeated treatments with iodine-131.

UNLABELLED: To estimate a cumulative dosimetric index that reflects the dose to the circulating lymphocytes after repeated treatments with 131I, biologic dosimetry was applied to 18 patients with differentiated thyroid carcinoma and neck relapse or lung metastases. METHODS: Chromosomal aberrations were scored in peripheral blood samples that were obtained before and 4 days after each administration of 3.7 GBq 131I according to two methods, conventional cytogenetics and chromosome 4 painting. RESULTS: The mean dosimetric index was equal to 0.5 Gy by both methods after the administration of 3.7 GBq 131I. Repeated administrations of 131I delivered the same dose each time, resulting in a cumulative dose from 1-3.5 Gy in the patients who had two to seven treatments. However, the estimated dose, based on the number of chromosomal aberrations on Day 4 and, above all, from the third treatment on, was considerably lower than the real dose absorbed by the lymphocytes. This may be linked to the phenomenon of apoptosis, which results in a loss of information during the course of repeated irradiation. CONCLUSION: Both chromosomal painting and conventional cytogenetics underestimate the cumulative dose after repeated 131I treatments. A complementary test measuring apoptosis may improve the dose estimates.

Sequential biological dosimetry after a single treatment with iodine-131 for differentiated thyroid carcinoma.

UNLABELLED: To determine the cytogenetic and genotoxic risk associated with therapeutic exposure to 131I (3.7 GBq) in 50 patients with differentiated thyroid carcinoma, we estimated the dosimetric index that reflects the dose to the circulating lymphocytes on Day 4 and at several time intervals after exposure over a period of 2 yr. METHODS: Chromosomal aberrations were scored in peripheral lymphocytes obtained before and then 4 days, 3 mo, 6 mo, 1 yr and 2 yr after the first administration of 3.7 GBq 131I according to two methods: conventional cytogenetics and chromosome 4 painting. RESULTS: The dosimetric index was 0.52 Gy on Day 4, 0.49 Gy at 3 mo, 0.45 Gy at 6 mo, 0.44 Gy at 1 yr and 0.42 Gy at 2 yr by conventional cytogenetics and 0.47 Gy on Day 4, 0.45 Gy at 3 mo, 0.44 Gy at 6 mo, 0.43 Gy at 1 yr and 0.42 Gy at 2 yr by chromosome 4 painting. We found a decrease in the frequency of chromosomal aberrations between Day 4 and 3 mo after exposure. This may be due to the decrease of lymphocyte counts shortly after 131I administration, which will recover later on. In contrast, the number of anomalies remained constant starting 3 mo after 131I administration. CONCLUSION: These techniques permit retrospective biological dosimetry for up to 2 yr after therapeutic exposure to 131I.