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FP5

Radiation-specific DNA non-double strand break lesions: repair mechanisms and biological effects (Non-DSB Lesions), Final report (summary)

Project ID: FIGH-CT-2002-00207
Funded under: FP5-EAECTP C

Abstract

To make rational judgements in radiation protection, it is necessary to extrapolate from the biological effects of radiation at low doses and low dose rates, and to have an appreciation of variation in response to ionising radiation (IR) among the human population. Therefore, a detailed knowledge of the basic mechanisms by which radiation induces cancer and genetic disorders is essential. DNA damage induced by ionising radiations is formed by direct energy deposition in DNA and by water radicals generated in the vicinity of DNA. The nature of ionising radiation-induced DNA lesions (such as 8-oxo-guanine, thymine glycols and single strand DNA breaks (SSBs)) overlaps substantially with lesions produced by endogenous oxidative metabolism in unirradiated cells. These endogenous damages are effectively repaired by the base excision repair (BER) pathway and this has led to suggest a threshold effect for radiation risk at low dose exposure. However, there is now clear evidence that the random energy deposition by IR not only induces isolated single DNA lesions but in addition a unique form of DNA lesions termed clustered DNA damage. This type of damage consists of two or more closely spaced lesions formed within about one helical turn in the DNA backbone and may include different combinations of base lesions and single strand breaks. The existence of clustered DNA damage caused by ionising radiation was first predicted from theoretical studies of radiation track structures and later demonstrated experimentally. The formation of clustered damage distinguishes ionising radiation-induced damage from normal endogenous damage. If processing of clustered DNA base damage differs from endogenous damage, then the linear-no threshold model might be the most appropriate model for the risk assessment of adverse effects of ionising radiation.

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Record Number: 8948 / Last updated on: 2008-02-13
Category: PRJS