Recombinant DNA Adviaory Committee - 09/14-15/92 
approximately 10 Roetgen units of chronic radiation, from both spontaneous and 
industrial exposure. The doubling dose for acute radiation is about l/40th of the chronic 
dose. One important issue is that risk of mutation is principally at the time of 
replication. Controlled experiments in which cell cycles are regulated in culture suggest 
that mutations occur when nucleotide substitutions are made at the time of cell division. 
Dr. DeLeon asked Dr. Neel to comment on the fact that the egg is responsible for about 
10% of chromosomal abnormalities. Dr. Neel said that at least 10% of newly fertilized 
eggs carry a major chromosomal abnormality, and that most of these are eliminated early 
in pregnancy. These abnormalities can be derived from either the father or the mother. 
Sperm cells transmit a large number of abnormalities. 
Mr. Capron asked if the current thrust of DNA research directed towards these questions 
still remain to be answered. Dr. Neel said more intensive investigation is needed using 
animals with short life spans. The carcinogenic implications of DNA therapy could be 
better addressed in animals with shorter life cycles. Mr. Capron asked if the 10% of 
abnormalities that occur result in neoplasms or growth deformities. How is fetal wastage 
taken into consideration in this figure? Dr. Neel said that genetic abnormalities occur in 
10% of transgenic mice having a gene inserted into their germ line. Dr. Anderson stated 
that the actual percentage could be higher than estimated. Dr. Neel explained that there 
is a range of abnormalities reported ranging from homozygous lethal in utero effects to 
physical abnormalities. 
Dr. Leventhal said that the data indicated that the offspring of individuals exposed to 
ionizing radiation were normal compared to control groups. Is there any evidence that 
future generations have a higher likelihood of being abnormal? Is there a protective 
effect of the radiation damage so that damaged cells are incapable of reproducing? Dr. 
Neel stated that the data suggests that the homeostatic properties of the genome are 
better than originally hypothesized. With regard to future generations, there is evidence 
of recessive hidden damage as evidenced by the presence of abnormal proteins. These 
studies are currently in progress at laboratories at Hiroshima and Nagasaki. Dr. 
Leventhal asked if there is a reason to suspect that the mechanism of alteration of DNA 
by gene therapy is more likely to result in transmissible damage that any other external 
source? Dr. Neel stated that cells have a coping mechanism that has evolved to 
compensate for radiation and chemical damage. Because there are multiple retroviral 
footprints in the human genome, a copying mechanism also exists to a degree. However, 
it is unclear what the cost to the population will be of randomly inserting genetic 
material into our genome. Dr. D. Miller interjected that there is a large body of data 
regarding the integration of transposable elements into genes in disease states such as 
Factor 8. Can any predictions be made regarding how often these integrations occur? 
Dr. Neel responded that data derived from Drosophila experiments suggest that 50% of 
all mutations are the result of retroviral movement. 
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Recombinant DNA Research, Volume 16 
