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