Recombinant DNA Advisory Committee - 09/14-15/92 
hours by spontaneous hydrolysis. Unless precisely replaced, each loss could result in a 
mutation. DNA is constantly exposed to mutagenic chemical radicals, resulting from 
indigenous and exogenous metabolism. These effects must be repaired exactly or a 
mutation will result. To meet these challenges, organisms have developed a complex 
array of fail safe mechanisms. Experiments demonstrate that E. coli is capable of 
repairing over 95% of the damage that occurs to its DNA. 
Dr. Neel presented a slide demonstrating the presence of rogue cells in human 
peripheral blood. Although the most abnormal of these rogue cells are not capable of 
undergoing mitosis, the less abnormal ones could be capable of cell division. It is 
postulated that these cells occur in other tissues of the body and may be the starting 
point of oncogenesis. Data suggests that these abnormal cells are the result of 
transposon activation. 
Dr. Neel addressed the effect of severe external perturbation, such as exposure to atomic 
bombs, on DNA. He noted a 46 year victim follow-up to the Hiroshima and Nagasaki 
bombings. This follow-up includes a complex epidemiological analysis of the individuals 
effected as well as their offspring. These data have been matched to control individuals 
with respect to sex and year of birth. Rosters (cohorts) exist that include data on 
approximately 30,000 offspring of the exposed individuals. In this group, the rate of 
untoward pregnancies and mortality exclusive of cancer is far below the level of 
statistical significance. Protein studies reveal no evidence of increased mutation rates. 
In addition, these data suggest that there was no effect on the physical development of 
these offspring. No change in the expected sex ratio was observed. No increased 
incidence of inheritable or non-inheritable tumors was observed. In summary, it has not 
been statistically demonstrated that parental exposure to the nuclear radiation resulting 
from these bombings has adversely affected the attributes of the children of the exposed 
individuals. 
Dr. Neel stated that for the past 40 years, data regarding the genetic implications of 
radiation have been guided by in vivo murine research. Presently, mutational geneticists 
are discovering that the human data derived from the acute exposure to radiation does 
not correspond to data derived in mice. The doubling dose of acute radiation for mice is 
approximately 0.4 severs. Humans are five times less sensitive to acute radiation than 
mice to radiation. For exposure to chronic radiation, the doubling dose is 1.0 severs for 
mice and 4.0 severs for humans. It is difficult to compare the human and murine 
findings. Therefore, mutation geneticists hypothesize that the only murine data that 
would compare to the human situation would be specific locus (phenotype) testing. 
Following this method of analysis, it was found that when the estimates of the acute dose 
in mice are converted to chronic dose by a dose rate factor of three, a doubling dose of 
4.0 severs is obtained. This result very closely estimates the human scenario. However, 
there are errors associated with these estimates. 
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Recombinant DNA Research, Volume 16 
