Anticlastogenic Effect in Human Lymphocytes by the Sodium Salt of 3,4-Secoisopimar-4(18),7,15-trien-3-oic Acid

The ability of the sodium salt of 3,4-secoisopimar-4(18),7,15-trien-3-oic acid (<b>1</b>), a diterpenoid obtained from <i>Salvia cinnabarina</i>, to inhibit the genotoxic effect of ethyl methanesulfonate (a clastogenic agent) and colcemid (an aneugenic agent), was studied using a micronucleus assay on cultured human lymphocytes. Cells were treated with <b>1</b> before (pretreatment), during (co-treatment), and after (post-treatment) treatment with the mutagens, in order to investigate the type of antimutagenic activity (desmutagenic or bioantimutagenic) manifested. In the range of concentrations tested (0.3–330 μM) <b>1</b> reduced significantly the frequency of micronuclei induced by ethyl methanesulfonate, in both pre- and co-treatment protocols (up to 74% and 70% of reduction, respectively), showing an anticlastogenic activity. Conversely, <b>1</b> did not inhibit the effect of colcemid in all treatments. The nuclear division index value of lymphocytes was not affected by treatment with <b>1</b>, thus demonstrating that the anticlastogenic effect of <b>1</b> was not due to a cytotoxic effect. On the basis of the results obtained, it can be hypothesized that <b>1</b> exerts its anticlastogenic activity against ethyl methanesulfonate by a desmutagenic mechanism, possibly by chemical inactivation of the mutagen