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Abstract
By binding covalently to DNA chemical mutagens and carcinogens inhibit replication, which can be measured as a decrease in thymidine incorporation into DNA. This DNA synthesis inhibition (DSI) has been determined in testicular cells of mice for a large number of compounds and has been found to correlate very well with their known mutagenic and carcinogenic properties.
Not only could this test give a qualitative answer about potential carcinogenicity or mutagenicity, but, with regard to its in vivo characteristics, could furthermore give an indication of the carcinogenic and mutagenic potency and thus be of use in the risk evaluation of chemical substances; the relationship between the DNA synthesis inhibition and the underlying alkylation of guanine ‐06 by different methylating agents is demonstrated.
As toxic effects decrease thymidine incorporation, too, means are discussed for distinguishing between “true”;, mutagenic, and “false”;, cytotoxic, DNA synthesis inhibition.
In conclusion, the implications of including the DSI‐test in a battery of mutagenicity tests are outlined.