42 



MAZIA: I think that one could challenge Dr. Barron's last point; 

 namely, that the irradiation effect is not on the nucleoprotein but on the enzyme 

 system synthesizing nucleoprotein by drawing upon a fundamental experimental 

 design in radiation genetics. One irradiates mature sperm in the male and ob- 

 serves a genetic effect of the radiation when the male is crossed with an unir- 

 radiated female. The sperm cell is not synthesizing nucleoprotein; this had 

 been synthesized some time earlier. The sperm nucleus carries a complete 

 genetic code that is waiting to be transported into an egg where it will go to work. 

 The fact that irradiation of the sperm nucleus does produce genetic effects - in 

 fact, irradiation of sperm is a favorite tool of the geneticist - tells us, I think, 

 that the nucleoprotein is, in fact, radiosensitive. In a way, the chromosomal 

 nucleoprotein appears to be the most radiosensitive of all systems. This may 

 be explained by the fact that the techniques of genetics and cytogenetics permit 

 us to observe effects at dose levels where you could not hope to do so on en- 

 zymes under physiological conditions. 



BARRON: I agree with Dr. Carter that we have just one parameter, 

 but you can do the same thing with amino acids. You irradiate amino acids and 

 you determine the diminution of the amino acids. You make a peptide. Immedi- 

 ately the deamination becomes more difficult. From the peptide you make a 

 protein. In other words, the more complicated the molecule becomes, the 

 greater its stability against the action of the ionizing radiation, because you have 

 the effect of steric hindrances and of electronegative groups in the protein mole- 

 cule, which protect the sensitive spot where the product of ionization is going to 

 act. 



MAZIA: The larger molecules may be more resistant to radiation ef- 

 fects that can be detected by chemical methods and yet be more sensitive in 

 terms of biological detection. They may have specificity and may be denatured 

 completely as a result of very minor structural modifications. In many cases, 

 such as the genetic system, there may be present only one or a few of a given 

 species of molecule, so that modification of one molecule will produce a large 

 effect biologically. Perhaps we should distinguish between the intrinsic stability 

 of molecules, which you have been discussing, and their stability in terms of the 

 probability that a radiochemical event will have measurable biological conse- 

 quences. 



CARTER: Of course, there are some aspects of organized systems, 

 such as Mazia has worked with, that deserve some comments. As I understand 

 them, the combination between nucleic acid and protein is an exquisitely sensi- 

 tive system in terms of certain parameters. 



MAZIA: Yes. Dr. Maurice Bernstein, working with Kauffman at Cold 

 Spring Harbor, has found that desoxyribonucleoprotein of nuclear origin shows a 

 sensitivity to X-rays beyond what would be predicted from information about ef- 

 fects on pure nucleic acids or pure proteins. 



HOLLAENDER: Carefully isolated nucleoprotein that has a very high 

 viscosity will respond by change in viscosity to less than 100 r. The ultraviolet 

 absorption spectrum will not change under such conditions. The sensitivity of 

 this nucleoprotein resembles the sensitivity of biological material toX radiation. 

 At least the energy values are of the same order of magnitude. (H). 



BARRON: I want to emphasize that when you irradiate two substances 

 you have not only the action of the ionizing radiation but you have also, the action 

 of the free radical that is produced when two systems are irradiated. I want to 

 extend this to the cell and to say that when you irradiate the cell, you produce. 



