Neoplastic Transformation Is Enhanced by Multiple Low Doses of Fission-Spectrum Neutrons

Abstract

The neoplastic transformation of C3H mouse 10T1/2 cells was measured induced by fission-spectrum neutrons delivered at a high dose rate in five fractions over 4 days. The transformation frequency was significantly enhanced over that due to single equivalent total doses. These new data, in the low dose region, demonstrate an increased transformation frequency by fractionated versus single exposures of high-dose-rate fission-spectrum neutrons; an increase equal to that observed with low-dose-rate fission-spectrum neutrons (i.e., 0.086 rad/min). Estimates of the dose modifying factor (DMF), based upon the ratio of the initial linear portions of the induction curves for high and for low dose rates, suggest the same DMF (approximately 7.8) for both five daily fractions of high-dose-rate neutrons and for low-dose-rate neutrons. However, when these results are compared to those following high-dose-rate 60Co gamma rays (100 rad/min), the relative biological effectiveness (RBE) for low-dose-rate fission-spectrum neutrons based upon slope ratios is 19.6; similarly, the RBE relative to five daily fractions of 60Co gamma rays is 78.8.

The Reverse Protraction Factor in the Induction of Bone Sarcomas in Radium-224 Patients

“…The observation of a reverse protraction factor for densely ionizing radiation is in line with a number of earlier experimental findings that suggest the possibility of enhanced effects of densely ionizing radiations in protracted or fractionated exposures (10)(11)(12)(13)(14). In human studies analogous relationships have been seen in uranium miners exposed to high levels of radon (75,17) and recently also in tin miners (18).…”

Enhanced Neoplastic Transformation Due to Protracted Exposures of Fission-spectrum Neutrons: Biophysical Model

“…Hill et al (1985) found that five equal fractions of high-dose-rate fission-spectrum neutrons, delivered over a 4-day period, resulted in transformation frequencies of 10TI/2 cells consistent with the results with low dose-rates that had been reported earlier ; Jones et al . (1989) obtained similar results with Syrian hamster embryo cells ; and Redpath et al (1990 a, b) also observed enhanced transformation with a human-cell hybrid .…”

“…As was noted by Elkind and Hill (1986 a), a prediction of the Rossi/Kellerer model is that cells exposed to multiple dose fractions, at a high dose-rate, should achieve a transformation frequency significantly lower than what was observed by Hill et al (1985) . In addition, the Rossi/Kellerer model did not explain why the induction curves for low-dose-rate and multiple high-dose-rate exposures converged on the curve for single high-dose-rate exposures at high total doses (Hill et al .…”

ras activation in human tumors and in animal model systems.

“…Both neutron and gamma irradiation are potential carcinogens, as demonstrated by the fact that both can transform cells in vitro (14)(15)(16) and induce tumors, including thymic lymphomas, in animals (17,18). One goal of this study was to determine whether the differences in qualities of these different forms of radiation might result in tumors with a different pattern of ras gene mutations.…”