Mutagens


Nature

A mutagen acts by changing the genetic material that is transferred to daughter cells when cell division occurs, with the result that the new cells have new inheritable characters. Such changes in the genetic material may consist of the alteration of one or more nucleotides, or of chromosomal alterations, resulting in an altered number of chromosomes or an altered chromosomal structure. If a mutagen acts on the germ cells (spermatozoa or ova) of man (or any other sexually reproducing organism) some of the offspring will carry the mutant genes in all their cells. The mutant may be so disadvantageous that death occurs before birth, and if this occurs at a very early stage of foetal growth, the pregnancy may not even be detected. If pregnancy goes to term, however, an abnormal offspring may be born, but the appearance of such an offspring is not in itself evidence that a new mutation has occurred, since abnormal offspring may be due to a mutation in previous generations or may be due to teratogenesis. A mutagen may also have an effect on somatic cells without necessarily affecting germ cells. In the latter case the mutated cell may die or it may be turned into a cancer cell. The resultant cancer cell does not necessarily develop into a clinically apparent tumour because other processes such as promotion and progression are also necessary. Some of these latter processes may also involve mutations. A gross similarity between mutagenesis and carcinogenesis can be said to exist, since both processes produce heritable changes in the phenotype. The current investigations on oncogenes, activated during tumorigenesis in humans, indicate a close connection between mutagenesis and (part of) carcinogenesis, although the precise relation is still unknown. Similar interference with the genetic material can apparently start up uncontrolled cell division. If the products of such division displace or invade normal tissues, the result is a cancer.

In both these instances, the mutagen responsible would have manifested activity as a carcinogen. A gross similarity between mutagenesis and carcinogenesis can be said to exist, since both these processes produce heritable changes in the phenotype.


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