X-ray dose rate and dose fractionation studies on mutation in Paramecium.

REVIOUS evidence has shown (KIMBALL, GAITHER and PERDUE 1957,1961; 'KIMBALL, GAITHER and WILSON 1959) that most of the X-ray induced mutations detected by inviability and slow growth after autogamy in Paramecium aurelia originate from reparable premutational lesions. These lesions are subject to repair until the chromosomes duplicate, and only then are they fixed as final mutation. Chromosomal breakage is a well-known form of lesion that is subject to repair by restitutional rejoining, but in the best-studied cases, rejoining of breaks appears to be independent of duplication. The earlier evidence for Paramecium, however, did not exclude the possibility that the mutational events in this organism arise mainly from breaks that can only restitute before duplication and can unite with independently produced breaks only at duplication. This alternative would be more plausible if the aberrations were really not the result of breakage and subsequent rejoining of the breaks, but came about by an exchange process between reparable lesions (REVELL 1959). Whatever the mechanism of interaction-lesion and exchange or breakage and rejoining-if chromosomal aberrations contribute to mutations, some of them should arise from two or more independent radiation events. This contribution should be decreased by fractionating the dose or by lowering the dose rate. Thus dose-rate and fractionation experiments should allow us to detect the mutagenic contribution by two-hit aberrations, to estimate its magnitude, and to measure the rate of disappearance of breaks by restitutional rejoining (or of exchangeinducing lesions by repair). It should then be possible to compare this rate with the previously measured rate of disappearance of premutational damage (KIMBALL et al. 1961), and from this comparison to decide whether the bulk of the premutational lesions could be the same as those producing two-hit aberrations. Such dose-rate and fractionation experiments have now shown that two-hit aberrations contribute to some extent to postautogamous inviability and slow growth. The bulk of the reparable premutational lesions, however, are repaired more slowly than those producing two-hit aberrations and must, therefore, be a different kind of lesion, quite possibly a precursor of true point mutation. A brief report of these findings along with a summary of our earlier findings on premutational damage has been given (KIMBALL 1963).