Cytogenetics in radiotherapy [II]

    Since the first observation on the induction of chromosome aberrations in blood lymphocytes of patients received radiotherapy by I. M. Tough, K. E. Buckton, A. G. Baikie and W. M. Court Brown in 1960 (Tough et al., Lancet, ii:849-851, 1960), lymphocyte chromosome aberration analysis rapidly expanded in varying area of radiation cytogenetics of humans exposed to ionizing radiation. Chromosome aberration analysis provides not only a quantitative measure of the biological effects of radiation in humans (IAEA Technical Report 2011; ISCN 2016) but also an important information in establishing correct clinical management in radiotherapy and radiation accident. The selective accumulation of iodine-131 (131I) in thyroid is an underlying strategy for the treatment of thyroid diseses with 131I. The selective accumulation of 131I released from nuclear power plant accident has been a major concern about the development of thyroid cancer in children after nuclear power plant accidents. Indeed, elevated level of chromosome aberrations have been found in Belarussian children after Chernobyl accident (e.g., Lehmann et al., Int. J. Radiat. Biol., 70:513-516, 1996; Zitzeisberger et al., Cancer Res., 59:135-140, 1999).

[2] Selective treatment of thyroid disease by iodine-131 (Blackwell et al. 1974) 

Reference
     Blackwell, N., Stevenson, A. C. and Wiernik, G. (1974): Chromosomal findings in patients treated with small doses of iodine-131. Mutation Res., 25:397-402.

Chromosome aberration analysis
     Chromosome analysis (48 h culture) has been performed on lymphocytes of 31 patients who had been treated with relatively small oral doses of 131I for hyperthyroidism. All patients received the tracer doses (2 μCi~8μCi of 131I) in a form of sodium iodine (Na131I). In three patients, chromosomes were also analyzed before treatment. Thyroid rate factors were determined by multiple urine samples over 24 h period.
     In these hyperthyroid patients, the mean activity of 131I ingested was 8.8 mCi (325.6 MBq). The whole-body dose from both β and γ radiation would be about 10.6 mrad (0.106 mGy).
     The observed chromosome aberration frequencies were far larger than expectation, suggesting a selective irradiation of lymphocytes.

Patient Sex Age No. of Dose Mean interval between No. of Chromosome aberrations Cells with indicated number of dics
ID (M/F) (year) treatments (mCi) dose and sampling (months) cells Dics cR 0 1 2 3
Post-treatment 2 F 60 1 7 8 100 0 0 100 0 0 0
4 F 65 1 5 18 100 0 0 100 0 0 0
7 F 70 3 16.5 54 200 2 0 198 2 0 0
8 F 73 1 8 46 100 0 0 100 0 0 0
9 F 52 1 5 15 100 3 0 99 0 0 1
10 F 45 1 6 19 200 4 0 196 4 0 0
11 F 49 2 18 11 200 0 0 200 0 0 0
12 F 66 1 12 144 200 0 0 200 0 0 0
13 F 82 3 23 50 200 0 0 200 0 0 0
14 F 49 2 12 7 200 0 1 200 0 0 0
15 F 67 2 10 4 300 5 0 297 2 0 1
16 F 68 1 5 36 100 0 0 100 0 0 0
17 F 49 1 8 72 100 0 0 100 0 0 0
18 M 69 1 7 60 100 5 1 96 3 1 0
19 M 42 1 5 8 100 0 0 100 0 0 0
21 F 55 1 7 19 100 1 0 99 1 0 0
22 F 76 1 5 33 100 2 0 98 2 0 0
23 F 75 1 8 72 200 1 0 199 1 0 0
24 M 43 1 5 2 200 0 0 200 0 0 0
25 F 76 3 22 158 200 1 0 199 1 0 0
27 F 76 1 10 24 200 1 0 199 1 0 0
28 F 29 1 5 15 100 1 0 99 1 0 0
29 F 51 1 8 1 200 4 0 196 4 0 0
30 F 68 1 5 24 200 1 0 199 1 0 0
31 M 42 2 20.5 160 200 3 0 199 0 0 1
33 F 80 1 5 1 100 2 0 99 0 1 0
36 F 42 1 5 1 100 6 0 96 2 2 0
45 F 67 1 5 1 100 2 0 98 2 0 0
6 F 67 1 5 1 100 6 0 96 2 2 0
3 F 80 1 5 1 100 2 1 99 0 1 0
5 F 42 1 5 1 100 2 0 98 2 0 0
Total 4,600 54 3 4,559 31 7 3
Pre-treatment 6 F 67 - - - 100 0 0 100 0 0 0
3 F 80 - - - 100 1 0 99 1 0 0
5 F 42 - - - 100 0 0 100 0 0 0
Total 300 1 0 299 1 0 0


Commentary: The dose distribution profiles revealing localized dose to lymphocytes. [A] Pre-treatment. [B] After oral administration of Na131I. EWBD: equivalent whole-bady dose (Gy-E).



[3] Selective treatment of thyroid disease by iodine-131 (Gundy et al. 1996) 

Reference
     Gundy, S., Katz, N., Fuzy, M. and Esik, O. (1996): Cytogenetic study of radiation burden in thyroid disease patients treated with external irradiation or radioiodine. Mutation Res., 360:107-113.

Chromosome aberration analysis
     This study was carried out in patients with thyroid cancer treated with different therapeutic modalities as, (A) patients received thyroidectomy only, (B) thyroid cancer patients were treated with 60Co γ-rays or X-rays (photon energy of 6 and 9 MV) following thyroidectomy, (C) patients undergoing thyroid ablation received 1734-2600 MBq Na131I orally, (D) patients with thyrotoxic disease (Basedow-Graves or toxic adenoma) in whom thyroid glands were remained intact and orally treated with 185-595 MBq Na131I. In addition, age and sex matched controls were also studied.

Subject category Surgical Radiological No. of Administration No. of cells Chromosome aberrations Distribution of cells with indicated number of dics+rings
treatment treatment subject observed Aberrant cells Chr.Frag Dics+rings Transloc. 0 1 2 3 4 5
Controls Healthy person none none 14 1,400 7 3 0 0 1400 - - - - -
[A] Thyroid cancer Thyroidectomy none 14 1,400 21 6 3 2 1398 1 1 - - -
[B] Thyroid cancer Thyroidectomy Eexternal γ- or X-rays** 7 50 Gy 700 173 68 196 1 566 90 32 7 4 1
[C] Thyroid cancer Thyroidectomy Radioiodine (Na131I oral) 12 1,734-2,600 MBq 1,200 33 7 12 2 1188 12 - - - -
[D] Thyrotoxic disease* none Radioiodine (Na131I oral) 8 185-595 MBq 800 40 22 18 5 787 9 3 1 - -
*) 3 Basedow-Graves and 5toxic denoma patients.
**) 5 patients received 60Co gamma-rays, and 2 patients received X-rays with 6 MV and 9 MV photons, respectively in daily fraction of 2 Gy of tumor dose.

Commentary: The dose distribution profiles. [A] Thyroidectomy only. [B] Thyroidectomy followed by gamma- or X-ray treatment. [C] Thyroidectomy followed by oral administration of Na131I.
                       [D] Intact thyroid glands + oral administration of Na131I. EWBD: equivalent whole-bady dose (Gy-E).