Neoplastic transformation in vitro and tumourigenicity in vivo are well correlated for x-rays but not for α-particles

The purpose of this study is to establish the relationship between radiation-induced oncogenic transformation as measured in vitro with the subsequent expression of tumourigenicity in vivo. Focus formation and the ability of transformed focus cells to reconstruct were compared with tumour formation following irradiation of C3H 10T1/2 mouse fibroblasts with 250 kVp X-rays and with plutonium-238 alpha-particles (energy, 3.26 ± 0.22 MeV; incident LET in water, 121 keV μm-1). It was found that the tumourigenicity of X-ray induced transformed foci was high (0.85, 95% CI: 0.69 - 0.95) while for alpha-particle induced foci this was significantly lower (0.39, 95% CI: 0.27 - 0.53). Focus reconstruction also demonstrates a good correlation with tumourigenicity for X-rays, but not for alpha-particles. One important consequence of these results is that the RBE of alpha-particles (and probably other radiations with high LET) for tumour formation is significantly lower than the RBE for oncogenic transformation. Possible mechanisms for this difference, involving delayed reproductive death, will be discussed. This observation has significant implications for the radiation weighting factors (wR) used in radiological protection. These are based on results from short-timescale in vitro endpoints such as chromosome aberrations and they may therefore be an overestimate compared with the true value for more delayed effects such as cancer induction