EFFECTS OF ALPHA-PARTICLES ON SURVIAL AND CHROMOSOMAL-ABERRATIONS IN HUMAN MAMMARY EPITHELIAL-CELLS

We have studied the radiation responses of a human mammary epithelial cell line, H184B5 F5-1 M/10. This cell Line was derived from primary mammary cells after treatment with chemicals and heavy ions. The F5-1 M/10 cells are immortal, density-inhibited in growth, and non-tumorigenic in athymic nude mice and represent an in vitro model of the human epithelium for radiation studies. Because epithelial cells are the target of alpha-particles emitted from radon daughters, we concentrated our studies on the efficiency of alpha-particles. Confluent cultures of M/10 cells were exposed to accelerated alpha-particles [beam energy incident at the cell monolayer = 3.85 MeV, incident linear energy transfer (LET) in cell = 109 keV/mu m] and, for comparison, to 80 kVp x-rays. The following endpoints were studied: (1) survival, (2) chromosome aberrations at the first postirradiation mitosis, and (3) chromosome alterations at later passages following irradiation. The survival curve was exponential for alpha-particles (D-0 = 0.73 +/- 0.04 Gy), while a shoulder was observed for x-rays (alpha/beta = 2.9 Gp; D-0 = 2.5 Gy, extrapolation number 1.6). The relative biological effectiveness (RBE) of high-LET a-particles for human epithelial cell killing was 3.3 at 37% survival. Dose-response curves for the induction of chromosome aberrations were linear for alpha-particles and linear-quadratic for x-rays. The RBE for the induction of chromosome aberrations varied with the type of aberration scored and was high (about 5) for chromosome breaks and low (about 2) for chromosome exchanges. The RBE for the induction of total chromosome aberrations (2.3 at 37% cell survival) was lower than that for cell survival, suggesting that chromosome damage at the first postirradiation mitosis is not sufficient to account for the increased efficiency of alpha-particles in the induction of lethal effects. However, measured cell survival after alpha-particle irradiation can be predicted from chromosome damage when cells at differ ent population doubling numbers after irradiation are considered. In fact, a high percentage of alpha-irradiated cells carried unstable chromosomal aberrations up to population doubling number about 5. On the other hand, x-ray-induced damage disappeared rapidly. These results suggest that alpha-particle-induced reproductive death of human mammary epithelial cells is caused by chromosome damage in the first 5 generations following exposure, whereas the inactivation produced by low-LET radiation is mostly related to the aberrations at the first post-irradiation mitosis.