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.
Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Edifici Cn, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.
M J
MJ
Ramírez
S
S
Puerto
P
P
Galofré
E M
EM
Parry
J M
JM
Parry
A
A
Creus
R
R
Marcos
J
J
Surrallés
D000328:Adult; D000368:Aged; D000483:Alleles; D002503:Centromere / Q000528:radiation effects*; D002869:Chromosome Aberrations; D019457:Chromosome Breakage; D002886:Chromosomes, Human, Pair 17 / Q000528:radiation effects*; D005260:Female; D017353:Gene Deletion; D016158:Genes, p53 / Q000528:radiation effects*; D006801:Humans; D006980:Hyperthyroidism / Q000532:radiotherapy; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D007457:Iodine Radioisotopes / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000166:cytology / Q000528:radiation effects / Q000648:ultrastructure*; D013964:Thyroid Neoplasms / Q000532:radiotherapy
D007457:Iodine Radioisotopes