Evidence that the [3H]thymidine-induced adaptive response of human lymphocytes to subsequent doses of X-rays involves the induction of a chromosomal repair mechanism.
When human lymphocytes are treated with [3H]thymidine ([ 3H]dThd), the observed number of chromosomal aberrations induced by [3H]dThd and subsequent doses of X-rays is less than the number induced by X-rays alone. Experiments in which cells were examined at various times after exposure to the X-rays showed that this phenomenon, termed an adaptive response to the endogenous radiation from tritium, is not an artefact caused by radiation-induced mitotic delays, which could result in the sampling of metaphase cells that were irradiated in different parts of the G2 phase of the cell cycle, where sensitivity to X-rays changes dramatically. Reconstruction experiments in which labelled female cells were co-cultured with unlabelled male cells now show that labelled and unlabelled cells progress to metaphase equally, and therefore that the adaptive response is not the result of selection against a radiosensitive population of cells that have incorporated [3H]dThd. Measurements of chromosomal aberrations induced in the labelled female cells and unlabelled male cells that had been co-cultured show that the adaptive response is restricted to those cells exposed to radiation from the incorporation of [3H]dThd and that diffusible factors are not involved. The results are consistent with the proposal that this adaptive response is the result of the induction of a hitherto unknown chromosomal repair mechanism. It has now been found that this repair mechanism is induced at levels of radiation from [3H]dThd that in themselves are too low to induce any discernible chromosomal aberrations and that its activity is dependent on the enzyme poly(ADP-ribose) polymerase, because 3-aminobenzamide, an inhibitor of poly(ADP-ribosyl)ation, prevents the adaptive response.
D000220:Adaptation, Biological; D000328:Adult; D001549:Benzamides / Q000494:pharmacology; D002869:Chromosome Aberrations; D004247:DNA / Q000096:biosynthesis; D004260:DNA Repair / Q000187:drug effects; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007399:Interphase; D008214:Lymphocytes / Q000187:drug effects / Q000528:radiation effects*; D008297:Male; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D013936:Thymidine / Q000378:metabolism / Q000494:pharmacology*; D014316:Tritium / Q000494:pharmacology*
D001549:Benzamides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D014316:Tritium; C025160:3-aminobenzamide; D004247:DNA; D013936:Thymidine