Alpha particle induced DNA damage and repair in normal cultured thyrocytes of different proliferation status.
Childhood exposure to ionizing radiation increases the risk of developing thyroid cancer later in life and this is suggested to be due to higher proliferation of the young thyroid. The interest of using high-LET alpha particles from Astatine-211 ((211)At), concentrated in the thyroid by the same mechanism as (131)I [1], in cancer treatment has increased during recent years because of its high efficiency in inducing biological damage and beneficial dose distribution when compared to low-LET radiation. Most knowledge of the DNA damage response in thyroid is from studies using low-LET irradiation and much less is known of high-LET irradiation. In this paper we investigated the DNA damage response and biological consequences to photons from Cobolt-60 ((60)Co) and alpha particles from (211)At in normal primary thyrocytes of different cell cycle status. For both radiation qualities the intensity levels of γH2AX decreased during the first 24h in both cycling and stationary cultures and complete repair was seen in all cultures but cycling cells exposed to (211)At. Compared to stationary cells alpha particles were more harmful for cycling cultures, an effect also seen at the pChk2 levels. Increasing ratios of micronuclei per cell nuclei were seen up to 1Gy (211)At. We found that primary thyrocytes were much more sensitive to alpha particle exposure compared with low-LET photons. Calculations of the relative biological effectiveness yielded higher RBE for cycling cells compared with stationary cultures at a modest level of damage, clearly demonstrating that cell cycle status influences the relative effectiveness of alpha particles.
Department of Oncology, Sahlgrenska Academy, University of Gothenburg, Sweden. Electronic address: madeleine.lyckesvard@oncology.gu.se.
Madeleine Nordén
MN
Lyckesvärd
Department of Oncology, Sahlgrenska Academy, University of Gothenburg, Sweden.
Ulla
U
Delle
Department of Oncology, Sahlgrenska Academy, University of Gothenburg, Sweden.
Helena
H
Kahu
Department of Radiation Physics, Sahlgrenska Academy, University of Gothenburg, Sweden.
Sture
S
Lindegren
The PET and Cyclotron Unit Copenhagen University Hospital, Rigshospitalet, Denmark.
Holger
H
Jensen
Department of Radiation Physics, Sahlgrenska Academy, University of Gothenburg, Sweden.
Tom
T
Bäck
Department of Medical Physics and Biomedical Engineering, Sahlgrenska University Hospital, Gothenburg, Sweden.
John
J
Swanpalmer
Department of Oncology, Sahlgrenska Academy, University of Gothenburg, Sweden.
Kecke
K
Elmroth
D000512:Alpha Particles / Q000009:adverse effects*; D000818:Animals; D001246:Astatine / Q000009:adverse effects; D002453:Cell Cycle / Q000528:radiation effects*; D002478:Cells, Cultured; D064447:Checkpoint Kinase 2 / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair / Q000528:radiation effects*; D048629:Micronuclei, Chromosome-Defective / Q000528:radiation effects*; D013552:Swine; D013961:Thyroid Gland / Q000378:metabolism* / Q000473:pathology
D064447:Checkpoint Kinase 2; D001246:Astatine
Alpha particle; DNA-damage; GammaH2AX; Radiation; Thyroid; pChk2