GENETIC EFFECTS 9 



If it can be satisfactorily determined directly, the whole-gamete effect is the measure most 

 immediately applicable for our purposes. The rates for specific loci are useful in indicating 

 absolute rates for both spontaneous and induced mutations. But their greatest value appears 

 to be in direct comparisons of mutation rates; for example, in comparisons of acute and 

 chronic radiation. Since there is evidence that different loci vary in their frequency of both 

 spontaneous and induced mutations, and not always in parallel, it is important to learn more 

 about the extent and nature of such inter-locus variability. It is important not only to investi- 

 gate point mutations at special loci but also structural changes of chromosomes of various 

 types in relation to cell type, stage of life cycle, and nature of radiation or other mutagenic 

 agent. 



There are clear indications that in the spermatogonia and oocytes of mice, chronic 

 irradiation is less effective in producing mutations than is the same total dose of acute radia- 

 tion. This difference does not appear to hold for mature spermatozoa. However, it should 

 be remembered that spermatogonia and oocytes are the cells that are most important in 

 human genetic hazards. Clearly it is important to learn more about such phenomena, for 

 they obviously bear directly on the problem of estimating the genetic hazards to man that 

 result from increased radiation exposure. Differences in effectiveness of chronic and acute 

 radiation make it important to re-examine the question of exact relation between induced 

 mutation values and radiation exposure. 



Although available evidence indicates that at relatively low radiation levels there is 

 little selective survival of unaffected mouse spermatogonial cells as compared with those 

 carrying mutations, differential multiplication of somatic cells may occur at radiation levels 

 high enough to produce appreciable numbers of gross chromosomal aberrations. Additional 

 and more refined measurements are clearly needed before it can be said under precisely what 

 conditions such selection occurs, and, when it does, what its genetic significance will be. 



More information is needed about the relationship between the mutation rates, spon- 

 taneous and induced, and the length of the life cycle. 



What kinds of organisms should be studied? For a long time to come, many of the 

 investigations can be carried out most effectively on experimental organisms such as bacteria, 

 molds, Drosophila, and mice. However, there are important points at which human statistical 

 data must provide key evidence, as for instance on the mutation rates of given genes and the 

 behavior of mutant genes in human population genetics. 



Additional work is also needed on the investigation of antimutagenic agents. There are 

 already clear indications that such agents do exist and that they can be effective either before, 

 during, or after exposure to radiation. We need to know much more about the action of these 

 substances. For example, do they influence nonradiation-induced mutation? Since such 

 agents are obviously of both theoretical and practical significance, it is important that their 

 further study be expedited. 



One of the difficulties in the study of the genetics of man is the small number of indi- 

 viduals available in any given pedigree. One possible way of avoiding this difficulty is through 

 the study of somatic mutations, where one can hope to deal with large populations of cells. 

 Here may be included studies on cell systems in the body (such as blood cells), cell cultures, 

 tissue cultures, and tumors. Human, other primate, and other mammalian tissue and organ 

 cultures are especially valuable in this connection. It has already been demonstrated that 

 chromosome breakage in varieties of human cells growing and dividing in tissue culture can 

 be related quantitatively to dosage. What we now need is comparative rates of radiation dam- 



