Induction of an Adaptive Response against Spontaneous Neoplastic Transformation In Vitro by Low-Dose Gamma Radiation

Abstract

An adaptive response against spontaneous neoplastic transformation in vitro induced by low-dose gamma radiation has recently been reported using a clone of C3H 10T1/2 cells with a predisposition toward spontaneous transformation (Azzam et al., Radiat. Res. 146, 369-370, 1996). To test the generality of this observation, the HeLa x skin fibroblast human hybrid cell system was used to look for such an adaptive response using a similar experimental protocol. In the experimental protocol used, the frequency of neoplastic transformation of unirradiated cultures (Arm A) was compared to that of cultures which had been irradiated with 1 cGy of gamma radiation and either plated immediately (Arm B) or held for 24 h at 37 degrees C prior to plating (Arm C) for assay of neoplastic transformation. The pooled data from four separate experiments demonstrated a significantly reduced transformation frequency for Arm C compared to Arms A and B. This is indicative of an adaptive response in the case of postirradiation holding, in agreement with the earlier study using C3H 10T1/2 cells. However, with the exception of one experiment, the existence of the adaptive response was not clear on the basis of analysis of individual experiments. This points out the importance of sample size when looking at low-dose effects that are close in magnitude to the inherent variations in spontaneous transformation frequency.

The Bystander Effect: Recent Developments and Implications for Understanding the Dose Response

“…Considerable additional data also indicate that, at low doses and dose rates of low Linear Energy Transfer (LET) radiation, the LNT assumption of linearity is invalid because risk is overestimated. All these other data show that low doses induce an adaptive response that reduces rather than increases risk at the molecular, cellular, and whole-animal levels (Olivieri et al, 1984;Azzam et al, 1992Azzam et al, , 1994aAzzam et al, , 1994bAzzam et al, , 1996Rigaud et al, 1993;Ishii et al, 1996;Redpath and Antoniono, 1998;Broome et al, 1999;Mitchel et al, 1999b), and does so at doses relevant to human occupational exposure. The mechanisms of these adaptive responses are the subject of intense investigation, but the discussion presented here implicates bystander effects as playing a large role in the adaptive response to radiation.…”

An Examination of Radiation Hormesis Mechanisms Using a Multistage Carcinogenesis Model

“…The dose rates considered in our studies are, however, much lower than the ones used by Azzam et al (1996) and Redpath and Antoniono (1998). Data on MN formation in human fibroblasts after various priming doses of ϕ-radition followed by a challenge dose show that any priming dose from 1 to 500 mGy (delivered at 1-3 mGy/min) produced the same drop in MN frequency (Broome et al, 2002).…”

“…Redpath and Antoniono (1998) showed that this occurred between 100 and 300 mGy for TF/SC in human cells. Azzam et al (1996) found that it was above 100 mGy in rodent cells.…”

“…In this section, the genomic instability model is extended to account for putative toxicant-induced adaptations in cellular repair systems as well as for toxicant-induced adaptations in the radical scavenging capacity of a cell. The experimental evidence suggesting the existence of radioprotective effects mainly comes from experiments performed with low doses of low-linear-energy-transfer (LET) radiation (e.g., Azzam et al, 1994aAzzam et al, , 1996Redpath and Antoniono, 1998;Redpath et al, 2001Redpath et al, , 2003aRedpath et al, , 2003bMitchel et al, 2003;Pant et al, 2003), and the proposed model may be more appropriate for-and X-rays than for high-LET radiations, such as α-particles from randon progeny.…”

Human Health and the Biological Effects of Tritium in Drinking Water: Prudent Policy through Science – Addressing the ODWAC New Recommendation

“…In cultured human cells, this protective effect was observed up to 24 hours after the low dose exposure, and longer in animal models. These low dose exposures have been shown to decrease the spontaneous levels of DNA damage, and spontaneous transformation frequency in different cell lines (Azzam et al, 1996;de Toledo et al, 2006;Redpath and Antoniono, 1998;Redpath et al, 2001). Recently the role of free radicals has been shown to be involved in low dose, low dose-rate, adaptive response mechanisms via oxidative metabolism and DNA repair.…”