36 Table 21 Frequency of Substitutionof Isoleucine for Other Amino Acids in Human*Hemoglobin From 23 Marshallese Subject No. and sex Age at Ageat Substitution exposure, yr present, yr frequency ( * 10-5) 3M 10M 18F 24F 33 F 1v2 30 24 13 ! 21 30 44 33 2k 19.79 3.58 5.06 13.45 4.94 42F 2 22 10.40 2! 21 23 51 6.98 12.93 4.04 3.65 813M 815M 929 F 836 M 839 F 841 F 846 F 867 F 868 F 20 24 35 41 46 4k 51 46 51 3.37 2.17 3.47 2.45 1.89 3.56 2.41 2.12 4:35 1547 F 1549 M 60 21 re) 1.57 Exposed, 175 R 35 F 7iF Exposed, 69 R 6M 8F 44M 45 F 81 F Unexposed 12 27 - 1 i¥2 3 31 7 944M A slight, but insignificant, increase in the isoleucine substitution frequency was found in controls 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 inindividuals exposed at youngerages, although the globin from subject No. 33, exposed at 1 year, had a low isoleucine content. The findings are consistent with the higher leukemiainduction, 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’9 include analyses showing (1) that higher isoleucine substi- 32 47 27 49 Average + SEM (x 10-5) 8.81+1.96 5.19 | 8.29 2.12 3.944 1.92 3.20 1.52 3.93 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 thesize of the irradiated human populations studied is probably too smallforit to be readily detected. The largest-scale human study was made by Neelet 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