II. Exposure to and effects of radiation.

III. Chemical mutagens.

IV. DNA repair.

Terms.

A. Electromagnetic radiation is a form of energy.
1. It has both wave-like characteristics, especially at low energy, and particle-like characteristics, especially at high energy. The energy level is inversely proportional to the wave length, i.e. long wave lengths have low energy; short wavelengths have high energy.

2. Examples of electromagnetic radiation are (in order of increasing energy):
radio waves, television waves, microwaves (radar), infrared radiation, visible light, ultraviolet light (UV), X rays, gamma rays, cosmic rays.

3. A particle of radiation is called a photon. At energies of visible light and greater, it is useful to treat radiation as a stream of discrete particles, each of which has a defined track.

B. Particulate radiation involves particles that have mass. As a result, they do much more damage than electromagnetic radiation for the same level of energy.
1. Electrons are very light and do relatively little damage.

2. Neutrons and protons are ca. 1800 times more massive than electrons and do correspondingly more damage.

3. Alpha particles are helium nuclei, which consist of two protons and two neutrons.

C. The various kinds of high energy electromagnetic and particulate radiation are produced by radioactive decay, atomic bombs, cathode ray tubes (TV), etc.

D. Radiation is often described as ionizing or nonionizing, depending on whether it has enough energy to knock an electron out of an atomic shell. Ionizing radiation can break covalent bonds; nonionizing radiation cannot. Ionizing radiation can cause mutations; nonionizing radiation cannot, except for ultraviolet light. X rays, gamma rays, cosmic rays, and all particulate radiation is ionizing.

E. Ultraviolet light causes mutations by increasing the energy of certain molecules, eg thymine, making them more reactive chemically. However, UV is absorbed so efficiently by water (and tissues), that none can reach the germ cells. It can only cause mutations near the skin surface.

A. Radiation is usually measured in rads or rems (old units; newer units are grays and sieverts. For most purposes, 1 rad = 1 rem = 0.01 sievert = 0.01 gray).

B. Humans are exposed to a number of sources of radiation, both natural and man-made.

1. Normal background radiation averages about 2,500 mrem (1 rem = 1000 millirems) per year. Major sources are:
a. Terrestrial: radioactivity of rocks and soil due to naturally occurring radioisotopes. Average exposure is about 28 mrem per year.

b. Cosmic rays from outer space average about 27 mrem per year

c. Internal naturally-occurring isotopes, mostly potassium-40, produce about 39 mrem per year.

d. Radon from decay of radium in soil averages 2,400 mrem per year, by far the largest source.

2. Major sources of man-made radiation are:
a. Medical X rays. The U.S. average is about 53 mrem per year.

b. Consumer products (TV sets, watches that glow in the dark, etc) average 10 mrem/year.

c. Exposure in U.S. from all other sources (fallout from bomb testing, air travel, etc.) is less than 1 mrem per year.

C. The biological effects of ionizing radiation can be measured by several endpoints.
1. Too much radiation leads to death. The LD₅₀ is the amount of radiation (or anything else) that kills 50% of the population. In the case of humans, the LD₅₀ is about 4.5 sieverts (450 rems).

2. Radiation is well established as a cause of most forms of cancer, due to enhancement of the rate of somatic mutations.

3. Radiation that penetrates the gonads can cause germinal mutations, capable of being transmitted to offspring.

a. A genetically significant dose of radiation is the amount that reaches the gonads multiplied by the probability of subsequent reproduction.

b. Both chromosomal rearrangements and point mutations are increased by radiation.

c. The amount of radiation that produces mutations equal in number to the spontaneous rate is called the doubling dose, estimated to be approximately 400 rem.

d. The yield of mutations versus radiation exposure is approximately linear down to moderate levels of radiation. However, the effects at very low levels are uncertain.

4. Radiation to embryos and fetuses can cause defects in development, especially of the central nervous system. Microcephaly and mental retardation can result.

D. Some human populations have received large radiation exposures.
1. The atomic bombs in Japan killed over 100,000 persons, primarily from the intense fireballs and shock waves. Many also died from excessive radiation. Among the survivors, there is increased risk of cancer, which is still observed. However, in spite of 45 years of careful search, no increase in mutations in the offspring of survivors has been found. Mutations must have occurred but at a frequency too low to detect.

2. The effects of Chernobyl have yet to be assessed. Unlike Japan, which involved acute radiation, the fallout from Chernobyl included very long-lived radioisotopes that concentrate in the bone marrow. The effects may ultimately be very bad, especially considering the millions of people exposed. An increase in microsatellite mutations has been observed in offspring conceived after exposure of their parents to Chernobyl fallout. The significance in terms of health is unknown.

3. Three Mile Island was a media event.

A. Everything we eat is composed of chemicals. Plants are remarkable chemists. Many of the chemical compounds they manufacture for their own purposes are highly mutagenic to humans.

B. There also are tens of thousands of man-made chemicals in the environment, many of which have not been tested adequately.

C. The choices to be made often involve competing risks. For example, should one use nitrite as a preservative in bacon and sausage and risk gastric cancer, or should one not use nitrite and risk death from botulism?

D. Unlike radiation, which penetrates readily to the germ cells, the route of exposure and the metabolism of chemicals can be very important.

1. Principal routes of exposure are food, inhalation, and absorption through skin.

2. Many substances are converted from nonmutagens to mutagens or vice versa by normal metabolism. Eg, benzpyrene in tobacco smoke.

3. In order to be mutagenic, a substance must go from outside a cell to the nucleus. Many substances cannot make this journey.

A. Excision repair involves enzymes that remove altered bases, such as thymine dimers or cytosine dimers.
1. Several hundred nucleotides of the affected strand are removed and replaced, using the normal strand as a template. Since this DNA synthesis occurs at times other than normal DNA replication, it is called unscheduled DNA synthesis and is a measure of exposure to certain types of mutagens, especially UV light.

2. There are several other DNA repair systems in humans, including direct repair. Each has its particular type of DNA damage that is repaired. All involve multiple enzyme steps and therefore are coded by multiple gene loci.

B. Several inherited defects in DNA repair systems are known, leading to high mutation rates in such persons.
1. Persons with xeroderma pigmentosum, an autosomal recessive disorder, have a defect in excision repair. They are ultra sensitive to sunlight and develop multiple skin cancers.

2. Other examples of inherited defects in DNA repair are Bloom syndrome, Cockayne syndrome, ataxia telangiectasia, and Fanconi anemia.

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