Fission-spectrum neutrons at reduced dose rates enhance neoplastic transformation

Hill, Colin K.; Buonaguro, Franco M.; Myers, C. P.; Han, A.; Elkind, M. M.

doi:10.1038/298067a0

Cited by 152 publications

(37 citation statements)

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“…Contrary to what had been observed for other end points such as cell killing the exposure of cells to fission neutrons at low dose rate (Hill et al, 1982(Hill et al, , 1984b, or to multiple-dose fractions at a high dose rate (Hill et al, 1985), resulted in an appreciable enhancement in the yield of transformants. As sketched in Figure 1, for doses larger than about 10 cGy the low doserate curve was concave downward and became coincident with the high dose-rate curve at 150-200 cGy.…”

Section: Neoplastic Transformation With Neutronsmentioning

confidence: 66%

“…We first reported in 1982 the anomalous enhancement of the rate of transformation of lOT1/2 cells when doses of fission neutrons were protracted in time (Hill et al, 1982). Contrary to what had been observed for other end points such as cell killing the exposure of cells to fission neutrons at low dose rate (Hill et al, 1982(Hill et al, , 1984b, or to multiple-dose fractions at a high dose rate (Hill et al, 1985), resulted in an appreciable enhancement in the yield of transformants.…”

Section: Neoplastic Transformation With Neutronsmentioning

confidence: 99%

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Enhanced risks of cancer from protracted exposures to X- or γ-rays: a radiobiological model of radiation-induced breast cancer

1996

Br J Cancer

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When exposures to sparsely ionising radiation such as X-or y-rays are protracted in time, generally the risk of radiationinduced cancer decreases. Qualitatively, a similar result has been observed for neoplastic transformation when the exposure of cells in vitro was protracted (Han et al., 1980;Hill et al., 1984aHill et al., , 1987. However, during the course of our studies in vitro with a densely ionising radiation, unexpected results were obtained: dose protraction led to enhanced transformation. To explain these results a cell-based model was developed (Elkind, 1991(Elkind, , 1992(Elkind, , 1994; a model that also explains enhanced tumorigenesis when doses of high-linear energy transfer (LET) radiation are protracted in time, as in the instance of the inverse relationship between lung cancer risk among uranium miners and radon concentration (e.g. Lubin et al., 1994). The formal properties of this model lead to the inference that, under certain circumstances, the protraction of doses of X-or y-rays could also increase rather than decrease the risk of cancer. In this editorial the radiobiology of the model and its supporting data are described as a basis for applying the model to the question of the increasing incidence of breast cancer. Neoplastic transformation in vitroIn the 1970s several groups initiated studies of radiationinduced neoplastic transformation in vitro. The end point that was used was focus formation of C3H mouse embryo lOT1/2, Balb/c 3T3 or Swiss 3T3 fibroblasts. These cells express postconfluence inhibition of cell division. Effective cell-to-cell communication results in the down-regulation of growth but not in transformed cells. Thus, densely staining discrete foci of piled-up cells, which had grown in the midst of a confluent layer of normal cells, were readily identified and scored.Because of a long-term interest in the role of repair processes in radiation-induced changes in mammalian cells, early in our work with IOT1/2 cells at the US Argonne National Laboratory we examined the role of repair of sublethal damage as well as damage subeffective in neoplastic transformation. With X-and y-rays, i.e. low linear energy transfer (low-LET) radiations, the effect of repair was examined by applying dose fractionation and/or the protraction of exposures in time via continuous, low doserate irradiation. Qualitatively, our results were consistent with tumour induction in animals. Even though sublethal damage (Elkind and Sutton, 1959) was effectively repaired in lOT1/2 cells (Han and Elkind, 1979), the concomitant repair of subeffective transformation damage resulted in a net

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Section: Neoplastic Transformation With Neutronsmentioning

confidence: 66%

Section: Neoplastic Transformation With Neutronsmentioning

confidence: 99%

Enhanced risks of cancer from protracted exposures to X- or γ-rays: a radiobiological model of radiation-induced breast cancer

1996

Br J Cancer

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“…Since the reports of Hill et al (1982Hill et al ( , 1984, some of the further studies with cells in culture confirmed an enhanced transformtion frequency due to protracted exposures to fission-spectrum neutrons and others did not . 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 .…”

Section: Introductionmentioning

confidence: 99%

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

Elkind

1991

International Journal of Radiation Biology

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“…61, NO . 2, Letter to the Editor Comment on mechanism of radiation effects with special reference to transformation (Received 8 August 1991) Interpretation of the observed enhanced frequency of neoplastic transformation of mammalian cells in vitro at low dose rates (Hill et al 1982) is an important problem, and the solution could have farreaching influence on our conceptual notions of biophysical processes in radiobiology . Hypotheses and proposed models for the effect have not yet led to a consensus (Hill et al .…”

mentioning

confidence: 99%

Comment on Mechanism of Radiation Effects with Special Reference to Transformation

Watt

1992

International Journal of Radiation Biology

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Fission-spectrum neutrons at reduced dose rates enhance neoplastic transformation

Cited by 152 publications

References 4 publications

Enhanced risks of cancer from protracted exposures to X- or γ-rays: a radiobiological model of radiation-induced breast cancer

Enhanced risks of cancer from protracted exposures to X- or γ-rays: a radiobiological model of radiation-induced breast cancer

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

Comment on Mechanism of Radiation Effects with Special Reference to Transformation

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