Oncogenic transformation of C3H 10T1/2 cells by acute and protracted exposures to monoenergetic neutrons

Abstract

An in vitro assay was used to assess cell killing and induction of neoplastic transformation in C3H 10T1/2 cells exposed to X rays and a range of monoenergetic neutrons administered at various dose rates. Curves for cell survival and induction of neoplastic transformation showed nonlinearity for cells exposed to acute graded doses of X rays, while irradiation of cells with 0.05 to 1.5 Gy of 0.23-, 0.35-, 0.45-, 0.70-, 0.96-, 5.90-, and 13.7-MeV neutrons resulted in a linear response as a function of dose for both neoplastic transformation and killing. When compared to results obtained with 250-kVp X rays, all neutron energies were more effective at both cell killing and induction of neoplastic transformation. When expressed as maximum biological effectiveness (RBEM), both cell survival and induction of neoplastic transformation showed an initial increase with neutron energy (maximal at 0.35 MeV), followed by a decrease in effectiveness with further increases in energy. These responses are consistent with microdosimetric predictions in that recoil protons from neutron interaction are shifted to lower lineal energies as neutron energies increase. To examine the effects of temporal distribution of dose on neutron-induced neoplastic transformation, cells were exposed to either a single dose or five equal dose fractions spread over 8 h. As a function of dose for single or fractionated exposures to 0.5 Gy or 0.23-, 0.35-, 0.45-, 5.9-, or 13.7-MeV neutrons, neither a sparing nor an enhancing effect was seen with survival. Similarly, the frequency of induction of neoplastic transformation was independent of dose fractionation for all but 5.9-MeV neutrons. The enhancing effects of exposure to fractionated doses of 5.9-MeV neutrons were further studied by comparing exposures for a range of doses given singly, in five fractions over 8 h, or continuously for 8 h. Results reaffirm the enhancing effects of dose fractionation on the induction of oncogenic transformation for 5.9-MeV neutrons. Within the limits of the data, there is modest enhancement of neutron-induced neoplastic transformation when the exposure dose is extended from a few minutes to several hours, with the enhancement being dependent on neutron energy.