36
Table 21
Frequency of Substitutionof Isoleucine for Other Amino Acids
in Human Hemoglobin From 25 Marshailese
Subject No. and sex
Age at
Age at
Substitution
exposure, yr
present, yr
frequency ( x 1075)
3M
10M
18 F
24F
33 F
142
30
24
13
1
21
30
44
33
21
19.79
3.58
3.06
13.45
4.74
42F
w1F
2
27
22
47
10.40
8.29
1
1%
3
31
7
21
21
23
31
27
6.98
12.93
4.04
3.65
2.12
20
24
35
41
46
41
51
46
31
49
3.37
2.17
3.47
2.45
1.89
3.56
2.41
2.12
4:33
3.93
al
4.57
Exposed, 175 R
35 F
Exposed, 69 R
6M
8F
44M
45 F
81F
Unexposed
12
-
813M
815M
929 F
836 M
839 F
841 F
846 F
867 F
868 F
944 M
1547 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 younger ages,
although the globin from subject No. 33, exposed
at | year, had a low isoleucine content. Thefind-
ings are consistent with the higher leukemia in-
duction, among persons exposedto x rays79 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
analyses showing (1) that higher isoleucine substi-
32
60
Average =
SEM (x 10-5)
8.812 1.96
5.19
5.94 1.92
3.20%1.52
TAS
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 aminoacid 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 forit to
be readily detected. The largest-scale human
study was made by Neel et 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