rte ee rn 2. Somatic Mutations In 1974, studies* were made of the frequency of amino acid substitution in the hemoglobin ofthe Marshallese on blood samples sent to Oak Ridge.75 Since there is no coded isoleucine’¢ in adult human hemoglobin A,its presence must be due to errors in transcription or translation or to somatic mutauonsarising during DNAreplication. Errors in transcription, which occur infrequently, form altered mRNA, tRNA, and rRNA; they change the coding in the mRNA and mayreduce the fidelity of the tRNA with regard to both theland.. | of amino acid it accepts and the mRNAeodons it. recognizes.’7Errors in translation’? arise through the attackagent of wrong amino acids totRNA (aminoaéyl synthetase errors) and the imprecise recognition of mRNA codons by tRNAanticodons (translational variation). Somatic mutations result from mistakes in replication of DNA; manysingle- base-substitution mutations change nonisoleucine into isoleucine codons,’® and the resulting mutant cells could have hemoglobin mRNAwithisoleucine codons. For this reason, an increase in theiso- Figure 25. Two-hit chromosomeaberrations in exposed Marshallese. Top: arrow points to dicentric form; bottom: arrow points to ring form.1* leucine content of hemoglobin A would be expected in humans exposed to agents causing basesubstitution mutations. Possibly radiation may cause base-substitution mutations in human so- matic cells, but this has never been established. >20) and 8 unexposed Rongelap people.* Chromosomeaberrations were noted in 23 of the exposed and in 5 of the unexposed Marshallese, but the exposed group had a numberof two-break aberrations (represented by dicentric chromosomes, translocations, and a ring form) that are thought to be associated with radiation exposure (Figure ~ Theisoleucine contentof the hemoglobin A was determined in blood from 13 exposed Marshallese and 12 unexposed. The frequency of isoleucine substitution for other aminoacids in hemoglobin was calculated by dividing the nanomoles ofisoleucine by the total nanomoles ofall other amino acids in each sample. The frequencies arelisted in Table 21. “These analyses were done by Drs. H. Lisco, New England Deaconess Hospital, and R.A. Conard, BNL. *These studies were done by Drs. R.A. Popp, G. P. Hirsch, and E.G.Bailiff at Oak Ridge National Laboratory. ae el ae o San “ewe, Maken:oe ne, ae fishermen,’ on victims of other radiation acci- dents.‘ and on Japanese bomb survivors. 74 ” 23).*! No two-hit aberrations were found in the unexposed group, but both groups had an unusual number of acentric fragments, the cause of which is not known. Paradoxically, Rongelap people with the lower exposure had more aberrations than those with the higher exposure. These studies indicate that a small but significant number of chromosomeaberrationspersisted in blood lym-phocvtes in some Marshallese as late as 10 years after exposure. The results are consistent with those of similar studies on the exposed Japanese sadist + Win ..)+ Dhaek ‘neaahe rngTe ramas were q@ 33