S-adenosyl-L-methionine is able to reverse micronucleus formation induced by sodium arsenite and other cytoskeleton disrupting agents in cultured human cells.
Deficiencies of folic acid and methionine, two of the major components of the methyl metabolism, correlate with an increment of chromosome breaks and micronuclei. It has been proposed that these effects may arise from a decrease of S-adenosyl-L-methionine (SAM), the universal methyl donor. Some xenobiotics, such as arsenic, originate a reduction of SAM levels, and this is believed to alter some methylation processes (e.g. DNA methylation). The aim of the present work was to analyze the effects of exogenous SAM on the micronucleus (MN) frequency induced by sodium arsenite in human lymphocytes treated in vitro and to investigate whether these effects are related to DNA methylation. Results showed a reduction in the MN frequency in cultures treated with sodium arsenite and SAM compared to those treated with arsenite alone. To understand the mechanism by which SAM reduced the number of micronucleated cells, its effect on MN induced by other xenobiotics was also analyzed. Results showed that SAM did not have any effect on the increase in MN frequency caused by alkylating (mitomycin C or cisplatin) or demethylating agents (5-azacytidine, hydralazine, ethionine and procainamide), but it reduced the number of micronucleated cells in those treated with agents that inhibit microtubule polymerization (albendazole sulphoxide and colcemid). Since albendazole sulphoxide and colcemid inhibit microtubule polymerization, we decided to evaluate the effect of SAM on microtubule integrity. Data obtained from these evaluations showed that sodium arsenite, albendazole sulphoxide, and colcemid affect the integrity and organization of microtubules and that these effects are significantly reduced when cultures were treated at the same time with SAM. The data taken all together point out that the positive effects of SAM could be due to its ability to protect microtubules through an unknown mechanism.
Ramírez
Tzutzuy
T
Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas, UNAM-Instituto Nacional de Cancerología, México, Mexico.
García-Montalvo
Verónica
V
Wise
Carolyn
C
Cea-Olivares
Raymundo
R
Poirier
Lionel A
LA
Herrera
Luis A
LA
D018053:Arsenites / Q000633:toxicity*; D002478:Cells, Cultured; D019175:DNA Methylation; D006801:Humans; D008214:Lymphocytes; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D012436:S-Adenosylmethionine / Q000494:pharmacology*; D017670:Sodium Compounds / Q000633:toxicity*
D018053:Arsenites; D017670:Sodium Compounds; C017947:sodium arsenite; D012436:S-Adenosylmethionine