RADIATION DAMAGE IN MOLECULES AND IN LIVING CELLS

From "Physics", Ohanian, 2nd Edition Expanded, Norton 1989, pp IV-7,8.

IV.4 RADIATION DAMAGE IN MOLECULES AND IN LIVING CELLS

Since biological tissues are composed of 70% to 90% water, most of the primary impacts of radiation on molecules will be impacts on water molecules. These impacts lead to the decomposition of water (radiolysis of water) and the subsequent formation of a variety of extremely corrosive molecules.

The first step is the decomposition of a water molecule by the impact of radiation; this results in a positive water ion and a free electron,

[radiation] + H2O -\ H2O+ + e- (9)

The electron travels some distance and is then captured by another water molecule;5 this results in a negative water ion,

e- + H2O+ -\ OH. + H+ (10)

Both the positive and the negative water ions (H2O+ and H2O-) are unstable; they dissociate into radicals and ions of hydroxyl and hydrogen,

H2O+ -\ OH. + H+ (11)

H2O- -\ OH- + H. (12)

These radicals OH. and H. are electrically neutral but they have "loose ends," that is, they have unsaturated chemical bonds; these radicals are therefore very eager to attach themselves to something -- they are very active.

(5 If the electron has sufficiently high energy, it can, of course, produce some ionization before it is captured.)

The reactive hydroxyl and hydrogen radicals attack the complicated organic molecules -- proteins, enzymes, nucleic acids -- that are the basic building blocks of living cells. Furthermore, by reacting with one another and with molecules of their environment, the hydroxyl and hydrogen radicals produce some other corrosive compounds that inflict additional damagfe on the organic molecules. The damage done to the organic molecules can take several forms: breakage of bonds, leading to fragmentation of the long molecular chains that serve as backbones for the molecules; rearrangement of bonds, leading to changes in the chemical behavior of molecules; and formation of extra bonds, leading to cross-linking either within one molecule or between neighbouring molecules. Such damage to the organic molecules in a living cell disrupts the normal chemical processes that sustain life. If the disruption is severe, the life of the cell ends.

Massive doses of radiation (many thousands of rads) can cause an almost immediate cessation of cellular metabolism followed by cellular disintegration. However, even a much smaller dose of radiation (a few hundred rads or less) can cause "reproductive death" of cells by destroying their ability to undergo cell division and to reproduce. Since the life of any complex organism depends on the continual replacement of old cells by new ones, the "reproductive death" of cells will ultimately bring about the phys iological death of the organism, even though the damaged cells continue to metablolize and, except for their inability to reproduce, may seem chemically and morphologicaly quite normal.

There exists considerable evidence that reproductive cell death is due to damage to the chromosomes of the cell -- specifically, damage to the DNA molecules within the chromosomes. DNA is the most crucial molecule in the cell; it is the molecule that contains all the information regarding the construction and operation of the cell, and it therefore directs all the processes within the cell. The DNA molecules and the chromosomes that contain them are both quite radiosensitive -- both DNA and chromosomes are subject to breakage when exposed to radiation. Furthermore, experiments show that even very low levels of radiation, which produce no overt morphological changes in the cell, iterfere with DNA sysnthesis and consequently inhibit cell division.

The sensivtivity of a cell to radiation depends on the phase of the life of the cell. The cell is most susceptible to suffer lethal damage if the radiation strikes it during the period of cell division (mitosis) just when the DNA and the chromosomes are attempting duplication. Obviously, cells that divide frequently are more likely to get caught in this delicate stage than cells that divide rarely or not at all. This leads to a general rule: the cells with the highest radiosensitivity are those that have t he highest rate of cell division (law of Bergonie and Tribondeau). For example, in mammals the cells in the bone marrow, lymphatic tissues, lining of the intenstine, ovaries and testes, and the cells in the embryo undergo very frequent cell divisions -- all these cells are very easily damaged by radiation. In contrast, the cells in the brain, muscles, bones, liver, and kidneys undergo little or no cell division -- these cells are relatively resisitant to damage by radiation.

The damage that a given absorbed fose of radiation inflicts on a tissue also depends on the kind of radiation. Some kinds of radiation, for instance alpha rays, are more efficient than others in damaging and killing cells. The kill efficiency of alpha rays is high because they produce very intense ionization along their path. When an alpha ray passes through tissues, it will damage many molecules in each cell; this concentrated damage is likely to have a lethal effect. The kill efficiency of gamma rays is much lower. When a gamma ray passes through the tissues, it will damage only a few molecules in each cell; hence the damage will be spread over a larger number of cells, and the injuries to individual cells are not as likely to be lethal. Injured cells have a chance to repair themselves gradually and recover.

Because of such differences in kill efficiency, the absorbed dose (in rads) is not a good indicator of the permanent biological damage. To obtain a measure of the biological damage, the absorbed dose must be multiplied by a correction factor that accounts for the kill efficiency of the radiaition. The correction factor is called the RBE (Relative Biological Effectiveness). Table IV.3 gives the RBE for diverse kinds of radiation; the values in this table are approximate because the exact RBE depends on the energy of the rays. The RBE of X rays is 1 by definition; according to table IV.3, alpha rays are 10 to 20 times more damaging than X rays, fast neutrons are 10 times more damaging than X rays, and so on.

TABLE IV.3 RBE Values

A reasonably good indicator of the biological damage in human tissues is the "equivalent" absorbed dose, which is the absorbed dose multiplied by the RBE:

["equivalent" absorbed dose] = RBE X [absorbed dose]

Since RBE is a pure number, the unit of "equivalent" absorbed dose is the same as that of absorbed dose (rads); however, in order to keep track of these two kinds of doses, the unit of "equivalent" absorbed dose is not written as rad, but as (_r_ad _e_quivalent _m_an). For example, if a human body receives a 100-rad absorbed dose of fast neutrons, the "equivalent" absorbed dose is 10 X 100 rems = 1000 rems (incidentally: this is an absolutely lethal dose). Note that doses of 100 rads of fast neutrons, 1000 rads of X rays, 1000 rads of gamma rays, and so on, all yield the same "equivalent" dose.

IV.5 THE PHYSIOLOGICAL EFFECTS OF RADIATION

The effect of radiation on man depends not only on the total "equivalent" dose, but also on how it is delivered. A dose that is delvered all at once (acute) is more dangerous than a dose spread oyt over a long period of time (chronic); a dose delivered to the entire volume of the body (whole-body exposure) is more dangerous than a dose delivered to a radiosensitive part of the body; a dose delivered to a radiosensitive part of the body (bone marrow, lymphatic tissue, gastrointenstinal tract) is more danger ous than a dose delivered to a radioresistant part (brain, muscles, bones, etc.).

Table IV.4 summarizes the effects of absorbtion of a whole-body dose delivered all at once. The information on radiation sickness and radiation death contained in this table is based on observations of the victims of the bombings of Hiroshima, Nagasaki, and Bikini atoll; observations of the victims of nuclear-reactor accidents; and extensive laboratory studies of animals subjected to irradiation.

TABLE IV.4 Effects of Acute Radiation Doses

___________________________________________________________________________
Dose(whole body) Critical organ      Effect              Incidence of death
___________________________________________________________________________
  0-100 rems     Blood               Some blood-         None
                                     cell destruction

100-200          Blood-forming       Decrease in white   None
                 tissue (bone marrow,blood-cell count
                 lymphatic tissue)

200-600          Blood-forming       Severe decrease     0-80% within
                 tissue              of white blood-     2 months
                                     cell count,
                                     internal hemorrhage,
                                     infection, loss of
                                     hair

600-1000         Blood-forming       Same                80-100% within
                 tissue                                  2 months

1000-5000        Gastrointestinal    Diarrhea, fever,    Nearly 100% within
                 tract               electrolyte         2 weeks
                                     imbalance

5000 and above   Central nervous     Convulsions,        100% within 2 days
                 system              tremor, lack of
                                     coordination,
                                     lethargy
___________________________________________________________________________

Doses between 100 and 200 rems produce radiation sickness, with nausea and vomiting. There is a reduction of the number of white blood cells due to damage to the bone marrow which generates these cells. If no secondary complications ensue, the victim recovers in a few weeks.

Doses from 200 to 600 rems lead to severe radiation sickness, with a possibly lethal outcome. A dose of 300 to 350 rems is sufficient to kill 50% of the exposed population if no medical treatment is available. With an exposure in this range there is severe damage to the bone marrow and a concomitant drastic reduction of the white blood-cell count; this renders the body very susceptible to infections.

Doses between 600 and 1000 rems are almost invariably fatal. Exposure at this level destroys the lining of the intestine; this eliminates the control of the body over its fluid balance, and also lays the interior of the body open to massive bacterial and viral invasion.

Doses of more that 5000 rems result in cerebral death by direct damage to the brain; at extreme doses, death can be nearly instantaneous.

Although low doses of radiation do not cause radiation sickness, they can cause other damage within the body. Irradtion of a pregnant woman, even at a low level, is likely to interfere with the normal development of the embryo. The embryonic tissues are extremely radiosensitive, and a dose of 15 rems or even less during the first 2 months of pregnancy may induce monstrous deformations of the embryonic organs.

Furthermore, radiation exposure produces delayed effects such as cancers, cateracts, and genetic defects, which only make their appearence years, or even generations, later. For example, among the survivors of the bombings in Japan, leukemia was two or three times as frequent as normally expected.

Even very small doses of radiation carry with them some risk of cancer. It has been estimated that a yearly dose of 200 millirems delivered to every inhabitant of the United States would lead to an average of 7100 extra cancer deaths each year. Besides, such doses of radiation increase the incidence of mutatiuons in cells, and therefore carry with them an increased risk of genetic defects. A yearly dose of 200 millirems delivered to every inhabitant of the United States would lead to an average of 6000 ext ra genetic defects in newborn children each year,

These numbers are directly relevent because they correspond to the average amount of radiation that inhabitants of the United States actually receive from various sources (see Table IV.5).

TABLE IV.5 Average Annual Radiation Doses per Inhabitant of the United States (from B. L. Cohen, Nuclear Science and Society.)

Note that one-third of the yearly dose is due to medical practice; this contribution could be substantially reduced (by a factor of two) by eliminating unnecessary diagnostic X-ray procedures and by restricting the size of the X-ray beam to the size of the film that is being exposed. Table IV.6 gives the doses received from various medical X-ray procedures.

TABLE IV.6 Radiation Doses from Diagnostic X Rays (from P. W. Laws and the Public Citizen Health Research Group, "The X-Ray information Book".)

[*]

This is the effective dose of whole-body exposures that produces the same average damage as the actual localized exposure of the target organ and the surrounding organs.

The maximum permissible dose for persons occupationally exposed to radiation -- radiologists, nuclear-reactor operators, experimental physicists -- has been arbitrarily set at 5 rems/year.