Prevention of aneuploidy by S-adenosyl-methionine in human cells treated with sodium arsenite.
Alterations in methyl group's metabolism affect availability of S-adenosyl-L-methionine (SAM); these modifications can be originated by enzyme polymorphisms, nutritional deficiencies, and exposure to chemical agents. There are several types of chemicals that interfere with methyl groups, among them is arsenic. It deserves special attention because it modifies a number of cell functions that influence the development of diseases such as cancer. Since part of arsenic's toxicity is influenced by changes on SAM availability, in a previous study we investigated whether exogenous addition of SAM to cells treated with sodium arsenite (NaAsO(2)) has an effect on its genotoxicity. Results demonstrated that SAM reduces the frequency of cells presenting micronuclei (MN) and tubulin-cytoskeleton defects after treatment with NaAsO(2). MN are fragments of the cell nucleus that may contain whole chromosomes or chromosome fragments depending on whether they derive either from the aneugenic or from the clastogenic action of chemicals. Therefore one question generated by these results was whether SAM reduced only the frequency MN resulting from aneugenic damage. To answer this question, in the present work we used an all-centromere DNA probe to distinguish the type of MN reduced by SAM after treatment with NaAsO(2) and vinblastine. In addition, the capacity of SAM to reduce clastogenicity was also evaluated. Results show that SAM decreases the frequency of cells with MN containing whole chromosomes in cultures treated either with NaAsO(2) or with vinblastine; however, induction of double-strand breaks by NaAsO(2) was not prevented by SAM.
Ramírez
Tzutzuy
T
Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México DF 04510, Mexico.
Stopper
Helga
H
Hock
Robert
R
Herrera
Luis A
LA
D000782:Aneuploidy; D018053:Arsenites / Q000633:toxicity*; D064007:Ataxia Telangiectasia Mutated Proteins; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism; D002478:Cells, Cultured; D002503:Centromere; D002869:Chromosome Aberrations; D004249:DNA Damage; D015342:DNA Probes; D004268:DNA-Binding Proteins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000633:toxicity*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D015162:Micronucleus Tests; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000494:pharmacology*; D012867:Skin / Q000166:cytology; D017670:Sodium Compounds / Q000633:toxicity*; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D018053:Arsenites; D018797:Cell Cycle Proteins; D015342:DNA Probes; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; C468783:H2AX protein, human; D006657:Histones; D017670:Sodium Compounds; D025521:Tumor Suppressor Proteins; C017947:sodium arsenite; D012436:S-Adenosylmethionine; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases