MAMMALIAN RADIATION GENETICS 141 



recessive visibles. Although no mutation rate could be calculated, Russell noted that 

 3 of the 5 new mutants affected a trait that was also controlled by one of the specific 

 recessive loci in the main test. Since 32 recessive visibles were uncovered in the same 

 group of animals, he therefore concluded that the mutation rate to dominant visibles 

 is probably significantly lower per roentgen than the rate for recessive visibles. 



Recessive visible mutations. — The determination of the mutation rate for recessive 

 visibles induced by irradiation at specific loci in mice has been one of the major research 

 efforts in radiation genetics by the Atomic Energy Commission for the past decade. 

 The results of this effort, along with the many ancillary findings, now constitute a major 

 contribution to our knowledge of genetics. This subject has been the topic of so many 

 discussions that the reader should properly address himself to the original reports. 

 The studies do provide some interesting sidelights on the problems of methodology, 

 however. The basic procedures for the specific-locus test (described above) enjoy the 

 economy of requiring only one generation of breeding to bring the progeny to test. 

 The spermatogonial mutation rate induced by single doses of X rays delivered at a rate 

 of90r per minute is approximately 25 x 10 _8 /r/genefor total doses up to 600 r. 1140, 1142 

 At 1,000 r, the rate falls to about one-half the above figure, which is interpreted to be 

 due to selection against a more radiosensitive class of spermatogonia. 1111, 1131 



The most significant finding, and the one which has received worldwide attention, 

 concerns the effect of the dose rate of radiation on the observed mutation rate. If the 

 exposure is delivered, essentially continuously, at rates of either 10 r/week or 90 r/week 

 (from 1 to 10 milliroentgens/minute), the mutation rate falls to about one-fourth that 

 observed following the single dose exposure. 1140, 1142 The difference is significant and 

 has also been confirmed for the female. 1126, 1139, 1143 The effect had also been noted 

 by Carter, 164 but, unfortunately, his data and experimental conditions could not 

 clearly substantiate the interpretation that an effect of dose rate existed, although it 

 was suggested. He was forced to compare the mutation rate following single dose 

 exposure in males with the rate induced by continuous exposure in females without 

 the benefit of the reciprocal comparison. 



The interesting side effect of this finding in mice was that it produced a great deal 

 of concern and some criticism among geneticists, all of whom had learned as a basic 

 principle that the mutagenic effect of radiation always acted additively, regardless of 

 the manner in which the radiation was delivered. The original data that suggested 

 an effect of dose rate did contain a few uncertainties to warrant some of the criticism. 

 The protracted exposures were provided by the radioisotope cesium- 137, which emits 

 a 0.7 Mev gamma ray. The ionization density is less than that for 250 kev X rays, and 

 an RBE of 0.8 or 0.9 might be required to make the physical parameters constant. 

 The standard errors of the initial data were quite large and point-by-point significance 

 testing gave no real assurance of a difference between high- and low-intensity exposure 

 except at the level of the 600 r dose. It should be recalled, however, that the original 

 concept of dose-rate independence was derived from data obtained on irradiated 

 Drosophila sperm. Analogous data derived from the exposure of mature germ cells 



