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By P. Turner

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Assays which reproduce some specific stage of the process of carcinogenesis. Tests for primary DNA damage are based upon the concept that mutagenic chemicals are capable of inducing lesions or structural changes in the DNA of an exposerl organism. In some cases the 35 specific DNA lesions induced may be identified, but this is not generally the case with the vast majority of potentially hazardous environmental chemicals . However, a fundamental property of those DNA lesions that initiate genetic damage is that they are susceptible to the action of cellular enzymes which are capable of removing the lesions and repairing the resultant gaps in the DNA by the replacement of the missing nuc leotides with new ones (figure 2).

52 A) FORM AND MEANS OF ADDITION Chemical I : 'V Chemical B) DRUG METABOLISING SYSTEM Binding to I ~ non-essential sites 1/ Active metabolite of chemical / ~ reversible endpoint Interaction with essential cellular or extra-cellular component ~ irreversible endpoint C) SYSTEM INTERFACE Fig. 3. D) RESPONSE SYSTEM Feature of an in vitro toxicity test. The means of addition of an agent to a test depends both on the type of agent and the nature of the test. The simplest method is to dissolve the sample into a suitable solvent.

These types of changes are illustrated in figure 1. Such changes in nucleotide sequence may lead to the production of proteins containing an abnormal sequence of amino acids (missense) or to the production of a non-coding triplet which leads to chain termination and the production of a shortened protein (nonsense). A'B'C'-A'B'C'-A'B 'C~ _a bc_ab c-a b c-a b c - I 2 3 4 - A A-A A-A A-A A Base subst itut ion DNA RNA prote in mutat ion ~change of base - A B C-A B C-A B D-A B C- A'B'C'-A'B'C'. A'B'D'-A'B'C'- -abc-abc-abd-abc- - ~ A A'-A A~A A~A A~ DNA RNA protein Framesh ift mutat ion .

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