BIOCHEMISTRY OF MUTAGENESIS

Mutagenesis is the phenomenon in which inheritable traits result from alterations of DNA.  Although mutation is a normally occurring process that gives rise to diversity in species, most mutations are harmful.  The toxicants that cause mutations are known as mutagens.  These toxicants, often the same as those that cause cancer or birth defects, are a major toxicological concern.

To understand the biochemistry of mutagenesis, it is important to know that DNA contains the nitrogenous bases adenine, guanine, cytosine, and thymine.  The order in which these bases occur in DNA determines the nature and structure of newly-produced RNA, a substance produced as a step in the synthesis of new proteins and enzymes in cells.  Exchange, addition, or deletion of any of the nitrogenous bases in DNA alters the nature of RNA produced and can change vital life processes, such as the synthesis of an important enzyme.  This phenomenon, which can be caused by xenobiotic compounds, is a mutation that can be passed on to progeny, ussually with detrimental results.

There are several ways in which xenobiotic species may cause mutations.  It is beyond the scope of this work to discuss these mechanisms in detail.  For the most part, however, mutations due to xenobiotic substances are the result of chemical alterations of DNA, such as those discussed in the example below.

Nitrous acid, HNO₂, is an example of a chemical mutagen that is often used to cause mutations in bacteria.  To understand the mutagenic activity of nitrous acid it should be noted that three of nitrogenous bases – adenine, guanine, and cytosine – contain the amino group. –NH₂.  The action of nitrous acid is to replace amino groups with doubly bonded oxygen atoms, thereby placing keto groups (C=O) in the rings of the nitrogenous bases and converting them to other compunds.  When this occurs, DNA may not function in the intended manner, causing a mutation to occur.

One of the more widely publicized mutagens is tris(2,3-dibromopropyl)phosphate, commonly called “tris”, that was used as a flame retardant in children’s sleepwear.  Tris was found to be mutagenic in experimental animals and metabolites of it were found in children wearing the treated sleepwear.  This strongly suggested that tris is absorbed through the skin and its uses were discontinued.

for further informations :

Manahan, Stanley E.; Toxicological Chemistry;