F. P. HUNGATE AND B. J. MCCLANAHAN 
901 
significant to the production of the multibreak 
aberrations most apt to be detected. From the 
present finding that swine chromosomes are rea- 
sonably sensitive to aberration induction, it 
seems most probable that failure to observe 
aberrations in the animals chronically exposed 
to 90Sr-"°Y is more likely due to the low dose 
rate than to insensitivity of the chromosomes. 
We have not as yet verified the appropriate- 
ness of 49 hours as the time of maximum ac- 
cumulation of first division metaphases in swine 
and humans. In fact, the recent observation of 
Bender and Brewen,'' indicating the presence of 
two or more dividing populations in phyto- 
hemagglutinin stimulated human leukocytes, 
makes this evaluation of division times even 
more important for comparative studies such 
as those we have just reported. 
REVIEW OF FACTORS AFFECTING 
ABERRATION FREQUENCY 
Chromosomes Critical to Cell Survival 
To comply with the symposium assignment, 
the following discussion will briefly identify 
some of the factors which modify the amount 
of chromosomal damage expected in studies 
such as those described above. Several reviews 
are available which cover topics relating to 
chromosome aberration more extensively than 
is appropriate here.*'-" 
Before proceeding, it may be useful to direct 
attention to early findings of Zirkle and Bloom 
and Rogers and von Borstel " that chromosomes 
are the structures critical to radiation induced 
cell death. This evidence has been repeatedly 
supplemented by a wide variety of cell survival 
data such as that of Puck et al. 12.13 ^nd Skargard 
et al.i* showing strong correlation of survival 
with aberration frequencies. While it is true 
that radiation induced lethality in cells such as 
the nondividing oocyte of young mammals 
does not appear to be explainable by chro- 
mosome breakage, most cell death following 
radiation correlates well with the frequency of 
chromosome aberration. From a variety of ob- 
servations, it is evident that induction of break- 
age and the resulting new chromosomal associa- 
tions are not of themselves lethal but become 
lethal when cells containing such aberrations 
undergo cell division. During the division proc- 
ess, information transfer to daughter cells is 
imprecise when aberrations lead to loss of 
acentric pieces, dicentric chromosomes with in- 
ternuclear bridges, duplications, etc. As the 
magntiude of such irregularity increases the 
probability of losing or compromising informa- 
tion critical to survival of subsequent cell gen- 
erations also increases. 
Aberration Types 
Chromosome aberrations have been produced 
by ionizing radiation both to provide material 
for genetic studies and to determine the manner 
by which aberrations are produced. If breakage 
occurs while the chromosomes are single, dele- 
tion type aberrations may be present in both 
chromatids and potentially present in both 
daughter cells. If the breakage occurs subse- 
quent to the S phase, when the chromosomes 
are split and called chromatids, the deletion is 
observed in only one of the two chromatids and 
would be expected to affect only one of the 
daughter cells. 
Chromosomal aberrations resulting from two 
breaks may involve a single chromosome in 
which case inversions or rings and deletions 
are produced. With techniques now available, 
inversions are not readily identified in mam- 
malian cells since only the order, not the 
amount, of genetic material in each chromosome 
changes. Ring shapes are readily identified and 
are categorized as a double break type. Also 
easily identified as a double break type are the 
chromosomes having two centromeres. These 
result from breaks in two different chromo- 
somes with rejoining in such a way that one 
of the portions has both centromeres, the other 
none. Equally likely are rejoinings with one 
centromere on each of the newly associated 
pieces. Recombinations involving more than 
one chromosome are termed translocations and, 
as with inversions, those combinations which 
result in all chromosomal materials attached to 
one and only one centromere have little effect 
on cell survival and are not readily identified. 
Rings and dicentrics in the metaphase stage are 
easily identified and signify multiple breakage. 
