Iodine-125-labeled DNA-Triplex-forming oligonucleotides reveal increased cyto- and genotoxic effectiveness compared to Phosphorus-32.
Int J Radiat Biol
; 92(11): 679-685, 2016 11.
Article
en En
| MEDLINE
| ID: mdl-27022855
ABSTRACT
PURPOSE:
The efficacy of DNA-targeting radionuclide therapies might be strongly enhanced by employing short range particle-emitters. However, the gain of effectiveness is not yet well substantiated. We compared the Auger electron emitter I-125 to the ß--emitter P-32 in terms of biological effectiveness per decay and radiation dose when located in the close proximity to DNA using DNA Triplex-forming oligonucleotides (TFO). The clonogenicity and the induction of DNA double-strand breaks (DSB) were investigated in SCL-II cells after exposure to P-32- or I-125-labeled TFO targeting the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene and after external homogeneous exposure to gamma-rays as reference radiation. MATERIALS ANDMETHODS:
TFO were labeled with P-32 or I-125 using the primer extension method. Cell survival was analyzed by colony-forming assay and DNA damage was assessed by microscopic quantification of protein 53 binding protein 1 (53BP1) foci in SCL-II cells.RESULTS:
I-125-TFO induced a pronounced decrease of cell survival (D37 at â¼360 accumulated decays per cell, equivalent to 1.22 Gy cell nucleus dose) and a significant increase of 53BP1 foci with increasing decays. The P-32-labeled TFO induced neither a strong decrease of cell survival nor an increase of 53BP1 foci up to â¼4000 accumulated decays per cell, equivalent to â¼1 Gy cell nucleus dose. The RBE for I-125-TFO was in the range of 3-4 for both biological endpoints.CONCLUSIONS:
I-125-TFO proved to be much more radiotoxic than P-32-TFO per decay and per unit dose although targeting the same sequence in the GAPDH gene. This might be well explained by the high number of low energy Auger electrons emitted by I-125 per decay, leading to a high ionization density in the immediate vicinity of the decay site, probably producing highly complex DNA lesions overcharging DNA repair mechanisms.Palabras clave
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Radioisótopos de Fósforo
/
Daño del ADN
/
Carcinoma de Células Escamosas
/
Apoptosis
/
Radioisótopos de Yodo
Límite:
Humans
/
Male
Idioma:
En
Revista:
Int J Radiat Biol
Asunto de la revista:
RADIOLOGIA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Alemania