Adaptive responses induced in vivo by low level tritium contamination

Single cells or whole organisms can often improve their ability to respond to a challenging irradiation after being previously exposed to a lower 'adaptive' amount of a similar stress. A consistent collection of experimental data exists proving that low doses of irradiation trigger adaptive responses in mammalian cells in vitro with respect to cell survival and mutation, induction of chromosome aberrations or micronuclei, DNA strand-breaks or synthesis of new proteins. Adaptive responses have been reported to occur also in vivo in bone marrow, blood cells and germ cells following low dose irradiation of animals. The investigated end-points have been the animal survival or cytogenetic effects. Doses used for the initiation of adaptive responses in vivo are within the range of 1-50 cGy with challenging doses between 0.75-6 Gy. Concerning the molecular mechanisms it is generally postulated that radioadaptation could result from activation of damage repair. Another hypothesis points to a mechanism related to the ability of cells to eliminate the toxic radicals generated through oxidative stress by the activation of antioxidant defense systems. It is however accepted that the upregulation of antioxidant defense is only partly responsible for the whole protection mechanism that governs the adaptive response. The alterations after in vivo irradiation appear to be dependent on the post-irradiation interval time and on the dose level. Very few information is available concerning the correlation between the radiosensitivity of cells or tissues and the capability to develop an adaptive reaction. Some new data were provided by our research group by examining whether adaptive response could be elicited in vivo by 7 or 35 cGy irradiation (low LET) delivered in a chronically regime (internal contamination of rats with tritiated water) and observed after subsequent 1 Gy high LET challenging irradiation (with fast neutrons). The end-points addressed to the evaluation of the oxidative state in different tissues and to the DNA biosynthesis going on in bone marrow. The lipid peroxides level in different tissues, the reduced glutathione content or glucose-6-phosphate dehydrogenase activity in erythrocytes, as well as the intracellular thymidine intake in the isolated bone marrow were proved to be rather sensitive experimental parameters in the characterization of in vivo effects produced by low dose and low dose rate contamination with tritiated water (HTO). Focussing on the relationship between tissue radiosensitivity and the putative expression of adaptive responses, the overall conclusion which could be claimed out was that the most radiosensitive tissues do not present an adaptive response at least concerning the antioxidant protection, whereas an adaptive like reaction is observed in the tissues with lower radiosusceptibility. For rats pre-exposed to tritiated water the lipid peroxides level was significantly decreased only for liver and kidney and only after the highest preirradiation dose. In erythrocytes the induction of a proper adaptive response is not observed but the data suggest that the antioxidant defense mechanisms are well controlling the oxidative status of the cell when the challenge neutron irradiation follows the low dose pre-irradiation. On the contrary, for small intestine and spleen, tissues of comparatively higher radiosensitivity, any adaptive induction has been observed in what concerns the production or depletion of lipid peroxides. In bone marrow, the thymidine incorporation assay has revealed a possible adaptive response for rats pre-exposed to 35 cGy although no such type of reaction was observed concerning lipid peroxides formation. The data are consistent with the assumption that there exist different recovery mechanisms caught by the two experimental parameters, mechanisms which evidently cooperate in the expression of the overall cellular resistance to radioinduced lesions. (authors)