Title: The 2007 Marie Curie prize: the linear no threshold relationship and advances in our understanding of carcinogenesis

Authors: Maurice Tubiana

Addresses: Faculte de Medecine, 45 Rue des Saints Peres, 75006 Paris, France

Abstract: Better knowledge of carcinogenesis has improved the assessment of the putative carcinogenic effects of low doses of Ionising Radiation (IR). Cancer induction is a main threat to multicellular organisms and safeguards have been introduced during evolution. Mutations result from endogenous agents, mainly Reactive Oxygen Species (ROS), and exogenous agents. IR and solar ultraviolet (UV) have existed since the onset of life and the existence of some congenital diseases, such as Xeroderma Pigmentosum (XP), demonstrates that without such defence mechanisms, life would have been impossible. Low doses of IR damage DNA but also activate cell defences: anti-oxidative mechanisms, DNA repair, adaptive responses, elimination of aberrant and preneoplastic cells, and immune reactions. The effectiveness of these defences decreases with the dose and is modulated by several time factors. The cell defence strategy varies with the dose, the irradiated volume and the damage inflicted on neighbouring cells. No cancer induction is detected in humans or animals for acute doses below 100 mSv. In patients treated by fractionated radiotherapy or submitted to iterative X-ray examination, the lowest dose that induces cancer appears to be at about 0.5 mSv, but doses as low as 20 mSv have a cumulative effect. Experimental studies, in vitro or on animals, suggest the existence of a threshold. In the low-dose range (< 100 mSv), epidemiological surveys do not bring any convincing data in favour of a Linear No Threshold relationship.

Keywords: dose-carcinogenic effect relationship; linear no threshold; LNT relationship; DNA repair; mutated cells elimination; intracellular signalisation; low radiation; ionising radiation; carcinogenesis; intercellular signalisation; oxidative stress; epidemiology; experimental data; cancer induction; Marie Curie prize.

DOI: 10.1504/IJLR.2008.020249

International Journal of Low Radiation, 2008 Vol.5 No.3, pp.173 - 204

Available online: 10 Sep 2008 *

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