36 Table 21 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 42F 71F Exposed, 69 R 6M 8F 44M 45 F 81F Unexposed 813 M 815 M 929 F Age at exposure. yr Age at present, yr Substitution frequency (x 10-5) vz 30 24 13 ! 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 1 1h2 3 31 7 21 21 23 51 27 6.98 12.93 4.04 3.65 2.12 20 24 35 3.37 2.17 3.47 836 M 839 F 841 F 846 F 867 F 868 F 944M 1347 F 1549 M 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 in individuals exposed at youngerages, although the globin from subject No. 33, exposed at | year, had a low isoleucine content. Thefindings are consistent with the higher leukemia induction, among persons exposed to x rays’? and to atom bomb irradiation,®° in those exposed prenatally and at youngages. 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’® include analyses showing (1) that higherisoleucine substi- 4} 46 2.45 1.89 60 7.15 41 51 46 51 49 2 Average = SEM(x 10-5) 8.81+ 1.96 3.94 1.92 3.20 1.52 3.56 2.41 2.12 4.35 3.93 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 thesize of the irradiated human populations studied is probably too small for it to be readily detected. The largest-scale human study was made by Neelet al. on the children of parents exposed in Hiroshima and Nagasaki,®! andit showed noclear-cut genetic effects. Examinations of the much smaller group of Marshallese