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PRINCIPLES OF TOXICOLOGY

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12.2 GENETIC FUNDAMENTALS AND EVALUATION <strong>OF</strong> GENETIC CHANGE 241<br />

Figure 12.1 Possible consequences of mutagenic event in somatic and germinal cells.<br />

organic compounds currently are in use, a number which increases annually. Only a very small fraction<br />

of these have been confirmed as human carcinogens (see Chapter 13), and no compound has been<br />

shown unequivocally to be mutagenic in humans. However, animal and bacterial tests have demonstrated<br />

a mutagenic potential for some occupational and environmental compounds at high exposure<br />

levels, and it is reasonable to consider human exposure to these compounds, particularly in occupational<br />

situations where contact may be frequent and/or intense. This is not to suggest that very small<br />

exposures common to environmental circumstances are likely to be associated with adverse effects.<br />

12.2 GENETIC FUNDAMENTALS AND EVALUATION <strong>OF</strong> GENETIC CHANGE<br />

Transcription and Translation<br />

DNA (deoxyribonucleic acid) is the structural and biochemical unit on which heredity and genetics<br />

are based for all species. It is the only cellular macromolecule that is self-replicating, alterable, and<br />

transmissible. Subunits of the DNA molecule are grouped into genes that contain the information,<br />

which is necessary to produce a cellular product. An example of such a cellular product is a polypeptide<br />

or protein, which may have a structural, enzymatic, or regulatory function in the organism. Figure 12.2<br />

illustrates how the sequence of messages on the DNA molecule is transcribed into the RNA (ribonucleic<br />

acid) molecule and ultimately is translated into the polypeptide or protein. The sequence of base pairs<br />

in the DNA molecule specifies the appropriate complementary (“mirror image”) sequence that governs<br />

the formation of the messenger RNA (mRNA). Transfer RNAs (tRNA), each of which is specific for<br />

a single amino acid, are matched to the appropriate segment of the mRNA. When the amino acids are<br />

released from the tRNAs and are linked in a continuous string, the polypeptide (or protein) chain is<br />

formed.<br />

Recognition of the mRNA regions by the tRNA-amino acid complex is accomplished by a system<br />

of triplet, or three-base, codons (in the mRNA) and complementary anticodons (in the tRNA). The<br />

critical features of this coding system are that it is simultaneously unambiguous and degenerate. In

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