Anticlastogenic effect in human lymphocytes by the sodium salt of 3,4-secoisopimar-4(18),7,15-trien-3-oic acid. 2012

Antonella Di Sotto, and Fabio Carbone, and Patrizia Hrelia, and Francesca Maffei, and Francesco Castelli, and Maria Grazia Sarpietro, and Gabriela Mazzanti
Department of Physiology and Pharmacology, "Sapienza" University , P.le Aldo Moro 5, 00185 Rome, Italy.

The ability of the sodium salt of 3,4-secoisopimar-4(18),7,15-trien-3-oic acid (1), a diterpenoid obtained from Salvia cinnabarina, 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 1 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) 1 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, 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 the anticlastogenic effect of 1 was not due to a cytotoxic effect. On the basis of the results obtained, it can be hypothesized that 1 exerts its anticlastogenic activity against ethyl methanesulfonate by a desmutagenic mechanism, possibly by chemical inactivation of the mutagen.

UI MeSH Term Description Entries
D008214 Lymphocytes White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS. Lymphoid Cells,Cell, Lymphoid,Cells, Lymphoid,Lymphocyte,Lymphoid Cell
D009153 Mutagens Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. Clastogen,Clastogens,Genotoxin,Genotoxins,Mutagen
D004224 Diterpenes Twenty-carbon compounds derived from MEVALONIC ACID or deoxyxylulose phosphate. Diterpene,Diterpenes, Cembrane,Diterpenes, Labdane,Diterpenoid,Labdane Diterpene,Norditerpene,Norditerpenes,Norditerpenoid,Cembranes,Diterpenoids,Labdanes,Norditerpenoids,Cembrane Diterpenes,Diterpene, Labdane,Labdane Diterpenes
D005020 Ethyl Methanesulfonate An antineoplastic agent with alkylating properties. It also acts as a mutagen by damaging DNA and is used experimentally for that effect. Ethylmethane Sulfonate,Ethyl Mesilate,Ethyl Mesylate,Ethylmesilate,Ethylmesylate,Mesilate, Ethyl,Mesylate, Ethyl,Methanesulfonate, Ethyl,Sulfonate, Ethylmethane
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012964 Sodium A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. Sodium Ion Level,Sodium-23,Ion Level, Sodium,Level, Sodium Ion,Sodium 23
D015162 Micronucleus Tests Induction and quantitative measurement of chromosomal damage leading to the formation of micronuclei (MICRONUCLEI, CHROMOSOME-DEFECTIVE) in cells which have been exposed to genotoxic agents or IONIZING RADIATION. Micronucleus Assays,Assay, Micronucleus,Assays, Micronucleus,Micronucleus Assay,Micronucleus Test,Test, Micronucleus,Tests, Micronucleus
D015394 Molecular Structure The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. Structure, Molecular,Molecular Structures,Structures, Molecular
D016587 Antimutagenic Agents Agents that reduce the frequency or rate of spontaneous or induced mutations independently of the mechanism involved. Anti-Mutagenic Agent,Antimutagen,Antimutagenic Agent,Anti-Mutagenic Agents,Anti-Mutagenic Effect,Anti-Mutagenic Effects,Antimutagenic Effect,Antimutagenic Effects,Antimutagens,Agent, Anti-Mutagenic,Agent, Antimutagenic,Agents, Anti-Mutagenic,Agents, Antimutagenic,Anti Mutagenic Agent,Anti Mutagenic Agents,Anti Mutagenic Effect,Anti Mutagenic Effects,Effect, Anti-Mutagenic,Effect, Antimutagenic,Effects, Anti-Mutagenic,Effects, Antimutagenic
D027544 Salvia A genus in the mint family (LAMIACEAE). Salvias

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