36 Table 2! Frequency of Substitution of Isoleucine for Other Amino Acids in Human Hemoglobin From 25 Marshallese Subject No. and sex Exposed, 175 R 3M 10M 18 F 24F 33 F 35 F 42 F 71F Exposed, 69 R 6M 8F +4 M. 45 F 81F Unexposed Age at exposure, yr Age at present, yr Substitution frequency (x 10-5) LH 30 24 13 1 12 2 27 21 30 44 33 21 32 22 47 19.79 3.58 3.06 13.45 4.74 5.19 10.40 8.29 L Lh2 21 21 6.98 12.93 51 27 3.63 2.12 3 31 7 813M 20 929 F 836 M 839 F 841 F 846 F 867 F 868 F 944 M 1547 F 1549 M 35 41 46 41 51 46 51 49 60 21 8I5M A slight, but insignificant, increase in the iso- leucine substitution frequency was found in con- trols aged between 20 and 51; the linear regression has a positive slope of 0.0234 x 10-5/year. Except for subject No. 1547, the higher frequencies were found in samples from exposed persons, but some of the exposed had values in the control range (Table 21). The higher frequencies were observed more often in individuals exposed at youngerages, although the globin from subject No. 33, exposed at | year, had a low isoleucine content. The findings are consistent with the higher leukemia induction, among persons exposed to x rays’? and to atom bomb irradiation,®° in those exposed prenatally and at young ages. Studies in progress strongly suggest that the increased isoleucine content in the hemoglobin of exposed Marshallese is due to base-substitution somatic mutations. The supporting data’5 include smnowing (1) that higherisoleucine substi- 5006133 23 24 Average = SEM ( x 10-9) 8,811.96 5.94=" 1.92 +.04 3.37 ; 3.202 1.52 2.17 3.47 2.45 1.89 3.56 2.41 2.12 4.35 3.93 7.15 1.57 tution frequencies occur in both the alpha and beta chains of hemoglobin from exposed persons, and (2) that contamination by fetal hemoglobin, which does contain isoleucine, could contribute no more than 7 parts per million amino acid residues to the values reported in Table 21. 3. Genetic Studies a. Possible Radiation Effects. The inheritance of radiation-induced mutations has been amply demonstrated in genetic studies on animals, butit has not been unequivocally seen in man. Large numbers of animals are necessary to demonstrate such an effect, and the size ofthe irradiated human populations studied is probably too small forit to be readily detected. The largest-scale human study was madeby Nee! et al. on the children of parents exposed in Hiroshima and: Nagasaki,®+ and it showed noclear-cut genetic effects. Examinations of the much smaller group of Marshallese