Aspects of the adaptive response to very low doses of radiation and other agents.

When human lymphocytes and other cells are pre-exposed to very low doses of ionizing radiation and subsequently exposed to a high dose, less genetic damage, i.e., fewer chromosome aberrations, is found than is observed in cells that had not been pre-exposed. This has been termed the adaptive response and has been attributed to the induction of a repair mechanism by the low dose exposure. Several experiments have now been carried out on this adaptive response to better characterize the phenomenon. (A) Experiments with differential display of mRNAs indicate that human lymphocytes exposed to 2 cGy of X-rays have somewhat different mRNAs expressed than do unexposed cells. This is providing access to DNA that might be involved in adaptation. (B) Other experiments with embryonic cells from transgenic mice that are deficient in superoxide dismutase (SOD) have shown that the adaptive response is unrelated to the amount of SOD in the cells, and thus is independent of superoxide radicals. (C) Experiments in which very low doses of various restriction enzymes were electroporated into human lymphocytes have shown that low levels of double-strand DNA breaks alone are able to induce the adaptive response. (D) Experiments in which human male lymphocytes (XY chromosome constitution) and human female lymphocytes (XX chromosome constitution) were cocultivated have shown that adaptation is not caused by a change in the rate of cell progression to mitosis after a challenge dose, and is a further indication that cell stage sensitivity is not a factor in the adaptive response.