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 (1), a diterpenoidobtained from Salvia cinnabarina, to inhibit the genotoxiceffect of ethyl methanesulfonate (a clastogenic agent) andcolcemid (an aneugenic agent), was studied using a micronucleusassay on cultured human lymphocytes. Cells weretreated with 1 before (pretreatment), during (co-treatment),and after (post-treatment) treatment with the mutagens, inorder to investigate the type of antimutagenic activity(desmutagenic or bioantimutagenic) manifested. In the range of concentrations tested (0.3−330 μM) 1 reduced significantlythe frequency of micronuclei induced by ethyl methanesulfonate, in both pre- and co-treatment protocols (up to 74% and 70% ofreduction, respectively), showing an anticlastogenic activity. Conversely, 1 did not inhibit the effect of colcemid in all treatments.The nuclear division index value of lymphocytes was not affected by treatment with 1, thus demonstrating that theanticlastogenic effect of 1 was not due to a cytotoxic effect. On the basis of the results obtained, it can be hypothesized that 1exerts its anticlastogenic activity against ethyl methanesulfonate by a desmutagenic mechanism, possibly by chemical inactivationof the mutagen.