Transformation of C3H 10T1/2 cells by low doses of ionising radiation: a collaborative study by six European laboratories strongly supporting a linear dose-response relationship

Abstract

For the assessment of radiation risk at low doses, it is presumed that the shape of the low-dose-response curve in humans for cancer induction is linear. Epidemiological data alone are unlikely to ever have the statistical power needed to confirm this assumption. Another approach is to use oncogenic transformation in vitro as a surrogate for carcinogenesis in vivo. In mid-1990, six European laboratories initiated such an approach using C3H 10T1/2 mouse cells. Rigid standardisation procedures were established followed by collaborative measurements of transformation down to absorbed doses of 0.25 Gy of x-radiation resulting in a total of 759 transformed foci. The results clearly support a linear dose-response relationship for cell transformation in vitro with no evidence for a threshold dose or for an enhanced, supralinear response at doses approximately 200-300 mGy. For radiological protection this represents a large dose, and the limitations of this approach are apparent. Only by understanding the fundamental mechanisms involved in radiation carcinogenesis will further knowledge concerning the effects of low doses become available. These results will, however, help validate new biologically based models of radiation cancer risk thus providing increased confidence in the estimation of cancer risk at low doses.

Detrimental and Protective Bystander Effects: A Model Approach

“…It is emphasized that the findings of Mill et al . (56) are not in contradiction to the data of Redpath et al . (15), Azzam et al .…”

“…In the current study, a biologically based multistage model for chromosome aberrations and in vitro neoplastic transformation has been tested on various data sets from cell culture studies. While the limitations of cell culture studies have been stated (56), one advantage is that they allow investigations of biological mechanisms that are relevant for human exposure at low doses. The current work focuses on two important low-dose effects that have been discovered in recent years: detrimental bystander effects (2–5) and protective apoptosis-mediated bystander effects (7, 20–23, 50).…”

“…(56) performed a collaborative study among six European laboratories using C3H 10T½ cells that were irradiated with X rays from 0.25 Gy to 5 Gy at 2 Gy/min. They concluded that the results clearly support a linear dose–response relationship for cell transformation in vitro with no evidence for a threshold dose (56). It is emphasized that the findings of Mill et al .…”

Protective Bystander Effects Simulated with the State-Vector Model

“…This has to do with the different dose rates applied, different experimental protocols including delayed plating and the fact H. Schöllnberger and P. M. Eckl that many of these other studies have a lowest dose that is too high to reveal any possible protective effects. For example, the lowest dose in the X-ray data by Mill et al (1998) is at 250 mGy while Redpath et al (2003) and Ko et al (2004) found the transition between protection and detriment from X-ray exposures at lower doses. This has been discussed in more detail by Schöllnberger et al (2002) and Schöllnberger et al (submitted).…”

What we know and what we don't know about cancer risks associated with radiation doses from radiological imaging

“…13 Perhaps, the most plausible in vitro model for radiation-induced cancer is in vitro oncogenic transformation, but, even for this, end point studies at doses ≤1 mGy are not feasible. 14,15 …”