Two in vitro tests for toxicological studies were introduced into and comparedby our companyČ Ames test (AT), which is a classical in vitro mutagenicity method, and Stress Promoters Induction Test, ...which is a new bacterial assay that was employed to improve the understanding of the toxicitymechanisms of tested compounds. In the latter test, the regulatory sequences of several stress genes are placed in front of the lac Z structural reporter gene whose product B-D-galactosidase can be readily measured. Mutagenicity and toxicity of a new nonsedating antihistamine that had previously shown moderate toxicity in animal studies were examined with both tests. None of the tested concentrations was mutagenic, but the antihistamine was toxic to Salmonella typhimurium tester strains in concentrations above 0.83 mM (1mgžplate). The mechanism of antihistamine toxicity was determined with the Stress Promoters Induction Test. On the basis of transcription from micF, osmY, dinD and soi28 promoters, it was presumed that the antihistamine acts on DNA topology. This was later confirmed with an in vitro test on gyraseactivity. The obtained results met our expectations about mechanistic potential of the new method that is based on measuring stress response events in organisms.
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