Two types of mutagens are considered here which are mostly affected the humans producing different mutations resulting in a number of abnormalities: 1. Radiation Exposure 2. Chemical Mutagenesis.
Type # 1. Radiation Exposure:
High energy radiation or ionising radiation produces a genetic alteration or mutation at a very low dose also. It has been shown experimentally that a low dose of X-ray (100R) will destroy a large part of the spermatogonia in male mammals resulting in sterility. Similarly, there is a high level of risk if fertilization occurs within the first few weeks after radiation exposure in human male.
In case of acute irradiation, generally two types of danger could occur:
(a) The immediate damage to the exposed person, which may be indicated by burns or other direct or secondary effects on the body tissues.
(b) The more insidious damage to the DNA in his/her reproductive cells which would affect the future generations.
Of the above two types of danger, the first one cannot be detected if the doses are on the magnitude of 50 mR (milliroentgens) but it may produce the second danger.
In this regard one important thing is to be remembered: the human female is more sensitive than the male in consequence with the effect of irradiation in the germ cells, because it has been shown experimentally that mature oocytes (about the time of fertilization) is particularly vulnerable to radiation.
The effect of dose rate of ionising radiation is also a very important one. A dose of radiation that is given over a longer period of time at a lower rate induces only 1/4th the number of recessive point mutations in oocytes and spermatogonia as the same dose given all at once; this is probably due to action of repair enzymes.
Therefore, it should be remembered that extended exposure at a lower dose rate is considerably less dangerous to human beings than a brief exposure with a high dose rate. Actually, from the genetical point of view, there is no safe dose of ionising radiation or, in other words, there is no such dose which can produce a threshold effect.
Another most important factor regarding the effects of ionising radiation on the rate of mutation is the oxygen tension and the temperature change. These two factors can enhance the effect of radiation-induced mutation frequency.
It has been generally found that low oxygen tension decreases the rate of mutations, or, in other words, oxygen can magnify the effect of radiation if it is present during the time of irradiation.
Oxygen has less effect with intense conditions than with moderate conditions of ionization. It is interesting to note that environmental agents that protect germ cells from radiation damage by lowering the oxygen concentration of the tissues.
Major Consequences with the Radiation Exposure:
1. Radiation damages the spermatogonia and the damaged germ cells could occur for a very long time, perhaps a lifetime.
2. Radiation also induces recessive and dominant point mutations.
3. Sometimes gross chromosomal damage may also occur.
4. Majority of the mutations after radiation exposure will be of recessive type and, therefore, not affect the phenotype in the first generation.
5. Mature oocytes are more susceptible regarding the radiation induced mutation than spermatogonia.
6. If conception has taken place shortly after radiation exposure it will be more dangerous.
Radiation Dose which will Induce the Mutations:
Following are the doubling dose (a doubling dose is the intensity of radiation necessary to double the normal spontaneous mutation rate in spermatogonia) for mice in pre- meiotic germ cell stage and may serve as a frame of reference to humans:
1. Dominant morphological mutations: 16- 26 R
2. Recessive mutations: 32 R
3. Autosomal recessive lethals: 51 R
4. Structural chromosomal aberrations: 31 R
Type # 2. Chemical Mutagenesis:
The effects of chemical mutagens are less easy to generalize about than those of the radiation mutagen.
One important thing is to be remembered that chemical mutagen is very stage specific and, accordingly, chemical mutagens can be classified into two classes:
(a) Chemicals which are mutagenic to both replicating and non-replicating DNA.
(b) Chemicals which are mutagenic only to replicating DNA. It has long been recognized that most of the strongly chemical mutagenic agents are also carcinogenic agents, because most of the geneticists agree that somatic mutation can cause cancer. There are a number of chemicals which can act as a potential mutagenic agent in humans and some of these chemicals are also used as drugs for curing some diseases.
Most of cytostatic, antimetabolite, hallucinogenic drugs and some antibiotics also act as potential mutagenic agents in normal therapeutic doses. Therefore, if a patient is treated with a high dose of an unusual or potentially dangerous drug, the doctor must take some careful measures like the recommendation of the use of contraceptives during the period of therapy and at least 8-10 weeks after the therapy etc..