Threshold-Type Dose Response for Induction of Neoplastic Transformation by 1 GeV/nucleon Iron Ions

Abstract

Neoplastic transformation of HeLa x skin fibroblast human hybrid cells by doses of 1 GeV/nucleon iron ions in the range 1 cGy to 1 Gy to exposed cultures has been examined. The data indicate a threshold-type dose-response curve with no increase in transformation frequency until doses above 20 cGy. At doses <10 cGy, not all exposed cells receive a direct traversal of an iron-ion track core, but all exposed cells receive up to several mGy of low-LET radiation associated with the delta-ray penumbra. It is proposed that the threshold-type response seen is a consequence of an adaptive response associated with the delta-ray exposure. For comparison purposes, the dose response for (137)Cs gamma rays over the same dose range was examined using the same experimental procedure. As we have shown previously, the dose response for (137)Cs gamma radiation was J-shaped. The iron ions were 1.5 to 1.7 times more biologically effective than the gamma radiation over the dose range examined.

Increased Frequency of Spontaneous Neoplastic Transformation in Progeny of Bystander Cells from Cultures Exposed to Densely Ionizing Radiation

“…They show a 2 to 3 fold-increase in neoplastic transformation in progeny of bystander cells (Table 1). This increase is similar to that induced in C3H 10T½ cells targeted by one or two á particles [41], and greater than that observed in HeLa x skin fibroblast cell line CGL1 directly targeted by 1 GeV/nucleon iron ions [26]. In the latter cells, an increase in the transformation frequency occurred at doses greater than 20 cGy to the exposed cell cultures.…”

“…The above results are opposite to the observations that exposure to low doses of γ rays, a radiation with low LET character, induces protective effects that reduce the transformation frequency to below the spontaneous level [24], [25]. In this context, during space travel or in the course of radiotherapy with HZE particles, low LET δ rays generated from HZE particle traversals may induce signaling events that trigger protective effects that may reduce the risk of neoplastic transformation [26]. Further, during space travel, δ rays are thought to traverse each cell in a human body about once per day [27].…”

Low-Dose Cancer Risk Modeling Must Recognize Up-Regulation of Protection

“…al. 2003;2008;Elmore et al 2009). In cultured cells a single low-dose, low-LET irradiation reduced neoplastic transformation to about 30 % of the transformation incidence in non-irradiated controls; and a threshold for neoplastic transformation existed in such cells even after high cell doses from accelerated particles (Azzam et al 1996;Elmore et al 2009).…”

Health Risks of Space Exploration: Targeted and Nontargeted Oxidative Injury by High-Charge and High-Energy Particles

“…The cross talks between signaling events induced by the dense and sparse ionizations are likely to have significant effects on the biological response. In cell populations exposed to low fluences of HZE ions, protective mechanisms (e.g., enhanced DNA repair, increased antioxidant potential) induced by low-LET secondary radiations may mitigate stressful effects propagated from adjacent cells traversed by primary particles (87). Conversely, the nonirradiated cells in the exposed population may transmit rescuing signals to the irradiated cells (56).…”

“…Thus, studies of transnitrosation and denitrosation of proteins with roles in antioxidation, DNA repair, and cell survival as a function of time after exposure to space radiation would be informative in elucidating the mechanisms underlying the development of genomic instability or induction of adaptive responses to the induced stress (179). They may identify biochemical events that underlie protective effects induced by low-LET space radiation, which defend against oxidative stress induced by densely ionizing HZE particles (87).…”