TY - JOUR
T1 - Toxicity and mutagenicity of selenium compounds in Saccharomyces cerevisiae
AU - Letavayová, Lucia
AU - Vlasáková, Danuša
AU - Spallholz, Julian E.
AU - Brozmanová, Jela
AU - Chovanec, Miroslav
N1 - Funding Information:
This study was funded by the VEGA Grant Agency of the Slovak Republic (Grant No. 2/6082/26).
PY - 2008/2/1
Y1 - 2008/2/1
N2 - Selenium (Se) is an essential trace element for humans, animals and some bacteria which is important for many cellular processes. Se's bio-activity is mainly influenced by its chemical form and dose. The use of Se supplements in the human diet emphasizes the need to establish both the beneficial and detrimental doses of each Se compound. We have evaluated three different Se compounds, sodium selenite (SeL), selenomethionine (SeM) and Se-methylselenocysteine (SeMC), with respect to their potential DNA damaging effects. The budding yeast Saccharomyces cerevisiae was used as a model system to test the toxic and mutagenic effects as well as the DNA double-strand breakage potency of these Se compounds in both exponentially growing and stationary yeast cells. Only SeL manifested any significant toxic effects in the yeast which were more pronounced in the exponentially growing cells than in those cells in the stationary phase of growth. The toxic effects of SeL were however accompanied with the pro-mutagenic effects in the stationary cell phase of growth. The toxic and mutagenic effects of SeL are likely associated with the ability of this compound to generate DNA double-strand breaks (DSB). We also show that SeL significantly increased frame-shift mutations, especially 1-4 bp deletions, in the CAN1 mutational spectrum of the yeast genome when compared to untreated control. We propose that SeL is acting as an oxidizing agent in S. cerevisiae producing superoxide and oxidative damage to DNA accounting for the observed DSB and cell death.
AB - Selenium (Se) is an essential trace element for humans, animals and some bacteria which is important for many cellular processes. Se's bio-activity is mainly influenced by its chemical form and dose. The use of Se supplements in the human diet emphasizes the need to establish both the beneficial and detrimental doses of each Se compound. We have evaluated three different Se compounds, sodium selenite (SeL), selenomethionine (SeM) and Se-methylselenocysteine (SeMC), with respect to their potential DNA damaging effects. The budding yeast Saccharomyces cerevisiae was used as a model system to test the toxic and mutagenic effects as well as the DNA double-strand breakage potency of these Se compounds in both exponentially growing and stationary yeast cells. Only SeL manifested any significant toxic effects in the yeast which were more pronounced in the exponentially growing cells than in those cells in the stationary phase of growth. The toxic effects of SeL were however accompanied with the pro-mutagenic effects in the stationary cell phase of growth. The toxic and mutagenic effects of SeL are likely associated with the ability of this compound to generate DNA double-strand breaks (DSB). We also show that SeL significantly increased frame-shift mutations, especially 1-4 bp deletions, in the CAN1 mutational spectrum of the yeast genome when compared to untreated control. We propose that SeL is acting as an oxidizing agent in S. cerevisiae producing superoxide and oxidative damage to DNA accounting for the observed DSB and cell death.
KW - DNA double-strand breaks
KW - Mutagenicity
KW - Saccharomoces cerevisiae
KW - Selenium compounds
KW - Sodium selenite
KW - Toxicity
UR - http://www.scopus.com/inward/record.url?scp=37849024376&partnerID=8YFLogxK
U2 - 10.1016/j.mrfmmm.2007.08.009
DO - 10.1016/j.mrfmmm.2007.08.009
M3 - Article
C2 - 17900630
AN - SCOPUS:37849024376
SN - 0027-5107
VL - 638
SP - 1
EP - 10
JO - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
JF - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
IS - 1-2
ER -