Response of EMT-6 Tumors to Single Fractions of X Rays and Cyclotron Neutrons: Evaluation and Comparison of Multiple Endpoints

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Abstract
EMT-6 [mouse mammary tumor] cells growing in vitro or as solid tumors were treated with single fractions of 250-kVp [peak] X-rays or cyclotron neutrons (21.5-MeV d+ on Be). The neutron RBE [relative biological effectiveness] for cell survival in vitro was 1.5-1.6 in the exponential region, less than the RBE of 1.8-2.5 for mitotic delay. The relatively greater delay produced by neutrons influenced cell progression and also response of survivors to subsequent doses of radiation in a manner different from that occurring after an X-ray dose isoeffective for cell killing. The in vivo endpoints of tumor response examined were clonogenic cell survival, local tumor control and growth delay. RBE for growth delay ranged from 2.3-2.4, but were not statistically significantly different from RBE for cure or clonogenic cell survival. The large neutron RBE of 3.0 for clonogenic cell survival at intermediate and high doses was based on apparent tumor hypoxia caused by anesthesia. The low neutron RBE of 1.7 for local control was due to immunosuppression caused by leakage and scatter neutron radiation to the animal''s body during localized treatment of the tumor; leakage and scatter whole-body photon exposure was negligible. Low-dose whole-body neutron irradiation reduces the TD50 [median target dose] in mice preimmunized with heavily irradiated tumor cells. This was consistent with the above explanation of the lowered RBE for local tumor control.