Alpha particle induced DNA damage and repair in normal cultured thyrocytes of different proliferation status

摘要

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 (2n At), concentrated in the thyroid by the same mechanism as1311 [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 (60Co) and alpha particles from211 At in normal primary thyrocytes of different cell cycle status. For both radiation qualities the intensity levels of 7H2AX decreased during the first 24 h in both cycling and stationary cultures and complete repair was seen in all cultures but cycling cells exposed to211 At. Compared to stationary cells alpha particles were more harmful for cycling cultures, an effect also seen at the pChl<2 levels. Increasing ratios of micronuclei per cell nuclei were seen up to 1 Gy 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.