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ADAPTATIVE RESPONSE TO RADIATION DAMAGE IN HUMAN LYMPHOCYTES INDUCED BY HYDROGEN PEROXIDE AND ITS MODULATION BY ANTIOXI- DANT AGENTS

Objective


Oxygen radicals may be responsible, not only for induction of cancer, but also for other degenerative diseases and for ageing. The formation of endogenous oxygen radicals, on the other hand, is an unavoidable natural process. Hydroxyl radicals are generated by ionising radiation. Since it has been demonstrated that exposure to low doses of some mutagens are protective for the cells when they are posttreated with higher doses (adaptive response) it is worth studying the response to ionising radiation after exposure to hydrogen peroxide.

Human lymphocytes pretreated with low doses of ionising radiation either from incorporated tritium or from X-rays become less susceptible to the chromosome damage induced by a subsequent irradiation with a higher dose of X-rays. This phenomenon is reminiscent of the adaptive response to alkylation damage reported in Escherichia coli. The response to alkylating agents, however, is known to be related to the induction of an alkyltransferase which cannot be responsible for the repair of radiation damage. For radiation protection, a good knowledge of the levels of exposure of human population to ionising radiation as well as the response of individuals to a given dose is necessary. Also, exposure of cells to low doses of mutagens deserves special attention because it probably more appropriately reflects the situation in natural environments.

Peroxides yield transient radical species that can damage deoxyribonucleic acid (DNA). Such partially reduced oxygen species are also generated by lethal ionising radiation and mutagenic ionising radiation. Low doses of hydrogen peroxide reduces the sensitivity of E. coli to a subsequent exposure to hydrogen peroxide or gamma-rays. Our results show the adaptive response after a single 30 minute pulse with hydrogen peroxide. The conditioning doses induced only a low frequency of aberrations. It therefore appears that low levels ofoxidative radicals that are produced by hydrogen peroxide, and migh t also be induced in water by low doses of X-rays, can induce the adaptive response in human cells. On the other hand, an explanation for the lack of adaptive response when the cells received multiple pulses with hydrogen peroxide prior to X-rays is not at hand, though the easiest explanation could be that the adaptive response becomes saturated after multiple conditioning insults.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

Universidad de Sevilla
Address
Profesor Garcia Gonzales
41012 Sevilla
Spain