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Evaluation of the genotoxicity of Cinnamon water extract
S106
Abstracts / Toxicology Letters 205S (2011) S60–S179
P1149 Role of metallothionein 2A polymorphism on lead metabolism: Are pregnant women with a heterozygote genotype for metallothionein 2A polymorphism and their newborns at risk of having higher blood lead levels? Z.
Kayaalti 1,∗ ,
D.
Tekin 2 ,
T.
was no increase at 312.5 and 625 g/ml. However, structural aberrations at the high dose were related to cytotoxicity from the CWE precipitate. Therefore, further study might be needed to evaluate the genotoxicity of CWE. doi:10.1016/j.toxlet.2011.05.384
Söylemezo˘glu 3
Forensic Genetic, Forensic Sciences, Ankara, Turkey, 2 Forensic Sciences, Ankara, Turkey, 3 Forensic Chemistry and Forensic Toxicology, Forensic Sciences, Ankara, Turkey
1
Numerous studies indicate that certain genetic polymorphisms modify lead toxicokinetics. Metallothioneins are protective against the toxicity of many metals, including lead. Placenta protects the fetus from certain toxicants, however, it can not prevent the fetus from exposure to lead, as this metal is able to cross the placental barrier easily. The aim of this study was to determine whether the maternal metallothionein 2A(MT2A)-5A/G single nucleotide polymorphism is related to the lead levels in maternal blood, placental tissue and the umbilical cord in 91 pregnant women and their newborns. Venous blood from the mother was collected to investigate lead levels and MT2A polymorphism. Cord blood and placenta were collected for lead levels. Analyses were made using an Atomic Absorption Graphite Furnace Spectrophotometer. Standard PCR-RFLP technique was used to determine MT2A polymorphism. Blood lead levels of heterozygote genotype mothers were statistically higher than those of homozygote genotype (p < 0.05). Maternal lead levels were significantly associated with umbilical cord lead levels for pregnant women with a homozygote genotype (p < 0.001). This association was not statistically significant for pregnant women with a heterozygote genotype. In contrast, the mean value of umbilical cord blood lead level for newborns with mothers of a heterozygote genotype was slightly higher than others but did not reach significance. No significant difference existed in placenta lead levels between both groups. This study suggests that pregnant women with a heterozygote genotype for MT2A polymorphism might have high blood lead levels and their newborns may be at risk of low-level umblical cord blood lead variation. doi:10.1016/j.toxlet.2011.05.383
P1150 Evaluation of the genotoxicity of Cinnamon water extract Y. Kim ∗ , J. You, J. Yoon, E. Cho, S. Kim, E. Kwon, B. Kang, J. Che Experimental Animal Research, Biomedical Research Institutes, Seoul National University Hospital, Seoul, Korea This study was conducted to evaluate the genotoxicity of Cinnamon water extract (CWE). In a bacterial reverse mutation assay, CWE was diluted in distilled water to 5 dosage levels of 312.5, 625, 1250, 2500 and 5000 g/plate. In an in vivo micronucleus assay, CWE was orally administered to 3 groups of 8-week-old male ICR mice at dosage levels of 0.5, 1 and 2 g/kg for 3 days. In an in vitro chromosome aberration assay, CWE was diluted to 3 dosage levels of 312.5, 625 and 1250 g/ml. In the bacterial reverse mutation assay, CWE did not induce mutagenicity in either Salmonella typhimurium or Escherichia coli with or without metabolic activation. In the mouse micronucleus test, there was no significant increase in the occurrence of micronucleus polychromatic erythrocyte. In the chromosome aberration test, chromatid breaks and exchanges were significantly increased at 1250 g/ml, but there
P1151 Genotoxicity assessment of the antimalarial compound artesunate in somatic cells of mice E.L. Maistro 1,∗ , I. Aquino 1 , F.F. Perazzo 2 1
Fonoaudiologia, Universidade Estadual Paulista (UNESP), Marília, Brazil, 2 Ciências Exatas E Da Terra, Universidade Federal de São Paulo (UNIFESP), Diadema, Brazil Artesunate is a derivate of artemisinin that is both an antimalarial agent and acts cytotoxically on tumor cells. Despite its therapeutic use, its in vivo genotoxic potential has still not been evaluated. This study, therefore, was an investigation into the genotoxic effects of a single oral administration of artesunate in cells of mice in vivo. Comet assay analysing leukocytes from peripheral blood and liver cells, and a micronucleus (MN) test of bone marrow cells from male Swiss mice were the assays used. The artesunate was administered by oral gavage at doses of 5, 50 and 100 mg/kg. Cytotoxicity was assessed by scoring 200 consecutive polychromatic (PCE) and normochromatic (NCE) erythrocytes (PCE/NCE ratio). The results demonstrate that artesunate induced significant DNA damage only in liver cells and that high doses of artesunate caused an increase in the mean number of micronucleated polychromatic erythrocytes (MNPCE). Under our experimental conditions, artesunate showed weak genotoxic effects at low doses and clastogenic effects at high doses. The PCE/NCE ratio indicated no cytotoxicity. The data obtained suggest caution about either continuous or high-dose use of artesunate by humans. doi:10.1016/j.toxlet.2011.05.385
P1152 Melatonin effects in lead acetate treatment on rats M. Martínez-Alfaro ∗ , D. Hernández-Cortés, A.J. Prado Torres, J.C. Rivera Leyva, D.O. Rocha, A. Cärabez-Trejo Pharmacy, Universidad de Guanajuato, Guanajuato, Mexico This study aims to investigate the role of melatonin, when it is administered to rats during periods in which the rats are exposed to low and high levels of lead acetate (10 and 100 mg/kg/day) for six weeks. Liver, bone marrow and kidney histopathological examinations were performed. MDA and lead blood level were assayed. DNA damage and DNA repair were evaluated in lymphocytes of the rats by comet assay. Lead exposure induces loss of weight in rats, increases MDA level in blood in a dose dependent manner. High lead doses induce genotoxic effects: DNA damage and slow DNA repair rate in lymphocytes. In this study co treatment with melatonin decreased the effect of lead on oxidative stress biomarker (MDA blood levels). Moreover, melatonin co treatment reduced the genotoxic lead effects (DNA damage and delay in DNA repair rate) induced by lead. These results demonstrate and strengthen the known role of oxidative stress in genotoxic effects of lead exposure. However, it should be noted that pathological examination with light microscopy showed only limited beneficial effect of melatonin
Abstracts / Toxicology Letters 205S (2011) S60–S179
P1149 Role of metallothionein 2A polymorphism on lead metabolism: Are pregnant women with a heterozygote genotype for metallothionein 2A polymorphism and their newborns at risk of having higher blood lead levels? Z.
Kayaalti 1,∗ ,
D.
Tekin 2 ,
T.
was no increase at 312.5 and 625 g/ml. However, structural aberrations at the high dose were related to cytotoxicity from the CWE precipitate. Therefore, further study might be needed to evaluate the genotoxicity of CWE. doi:10.1016/j.toxlet.2011.05.384
Söylemezo˘glu 3
Forensic Genetic, Forensic Sciences, Ankara, Turkey, 2 Forensic Sciences, Ankara, Turkey, 3 Forensic Chemistry and Forensic Toxicology, Forensic Sciences, Ankara, Turkey
1
Numerous studies indicate that certain genetic polymorphisms modify lead toxicokinetics. Metallothioneins are protective against the toxicity of many metals, including lead. Placenta protects the fetus from certain toxicants, however, it can not prevent the fetus from exposure to lead, as this metal is able to cross the placental barrier easily. The aim of this study was to determine whether the maternal metallothionein 2A(MT2A)-5A/G single nucleotide polymorphism is related to the lead levels in maternal blood, placental tissue and the umbilical cord in 91 pregnant women and their newborns. Venous blood from the mother was collected to investigate lead levels and MT2A polymorphism. Cord blood and placenta were collected for lead levels. Analyses were made using an Atomic Absorption Graphite Furnace Spectrophotometer. Standard PCR-RFLP technique was used to determine MT2A polymorphism. Blood lead levels of heterozygote genotype mothers were statistically higher than those of homozygote genotype (p < 0.05). Maternal lead levels were significantly associated with umbilical cord lead levels for pregnant women with a homozygote genotype (p < 0.001). This association was not statistically significant for pregnant women with a heterozygote genotype. In contrast, the mean value of umbilical cord blood lead level for newborns with mothers of a heterozygote genotype was slightly higher than others but did not reach significance. No significant difference existed in placenta lead levels between both groups. This study suggests that pregnant women with a heterozygote genotype for MT2A polymorphism might have high blood lead levels and their newborns may be at risk of low-level umblical cord blood lead variation. doi:10.1016/j.toxlet.2011.05.383
P1150 Evaluation of the genotoxicity of Cinnamon water extract Y. Kim ∗ , J. You, J. Yoon, E. Cho, S. Kim, E. Kwon, B. Kang, J. Che Experimental Animal Research, Biomedical Research Institutes, Seoul National University Hospital, Seoul, Korea This study was conducted to evaluate the genotoxicity of Cinnamon water extract (CWE). In a bacterial reverse mutation assay, CWE was diluted in distilled water to 5 dosage levels of 312.5, 625, 1250, 2500 and 5000 g/plate. In an in vivo micronucleus assay, CWE was orally administered to 3 groups of 8-week-old male ICR mice at dosage levels of 0.5, 1 and 2 g/kg for 3 days. In an in vitro chromosome aberration assay, CWE was diluted to 3 dosage levels of 312.5, 625 and 1250 g/ml. In the bacterial reverse mutation assay, CWE did not induce mutagenicity in either Salmonella typhimurium or Escherichia coli with or without metabolic activation. In the mouse micronucleus test, there was no significant increase in the occurrence of micronucleus polychromatic erythrocyte. In the chromosome aberration test, chromatid breaks and exchanges were significantly increased at 1250 g/ml, but there
P1151 Genotoxicity assessment of the antimalarial compound artesunate in somatic cells of mice E.L. Maistro 1,∗ , I. Aquino 1 , F.F. Perazzo 2 1
Fonoaudiologia, Universidade Estadual Paulista (UNESP), Marília, Brazil, 2 Ciências Exatas E Da Terra, Universidade Federal de São Paulo (UNIFESP), Diadema, Brazil Artesunate is a derivate of artemisinin that is both an antimalarial agent and acts cytotoxically on tumor cells. Despite its therapeutic use, its in vivo genotoxic potential has still not been evaluated. This study, therefore, was an investigation into the genotoxic effects of a single oral administration of artesunate in cells of mice in vivo. Comet assay analysing leukocytes from peripheral blood and liver cells, and a micronucleus (MN) test of bone marrow cells from male Swiss mice were the assays used. The artesunate was administered by oral gavage at doses of 5, 50 and 100 mg/kg. Cytotoxicity was assessed by scoring 200 consecutive polychromatic (PCE) and normochromatic (NCE) erythrocytes (PCE/NCE ratio). The results demonstrate that artesunate induced significant DNA damage only in liver cells and that high doses of artesunate caused an increase in the mean number of micronucleated polychromatic erythrocytes (MNPCE). Under our experimental conditions, artesunate showed weak genotoxic effects at low doses and clastogenic effects at high doses. The PCE/NCE ratio indicated no cytotoxicity. The data obtained suggest caution about either continuous or high-dose use of artesunate by humans. doi:10.1016/j.toxlet.2011.05.385
P1152 Melatonin effects in lead acetate treatment on rats M. Martínez-Alfaro ∗ , D. Hernández-Cortés, A.J. Prado Torres, J.C. Rivera Leyva, D.O. Rocha, A. Cärabez-Trejo Pharmacy, Universidad de Guanajuato, Guanajuato, Mexico This study aims to investigate the role of melatonin, when it is administered to rats during periods in which the rats are exposed to low and high levels of lead acetate (10 and 100 mg/kg/day) for six weeks. Liver, bone marrow and kidney histopathological examinations were performed. MDA and lead blood level were assayed. DNA damage and DNA repair were evaluated in lymphocytes of the rats by comet assay. Lead exposure induces loss of weight in rats, increases MDA level in blood in a dose dependent manner. High lead doses induce genotoxic effects: DNA damage and slow DNA repair rate in lymphocytes. In this study co treatment with melatonin decreased the effect of lead on oxidative stress biomarker (MDA blood levels). Moreover, melatonin co treatment reduced the genotoxic lead effects (DNA damage and delay in DNA repair rate) induced by lead. These results demonstrate and strengthen the known role of oxidative stress in genotoxic effects of lead exposure. However, it should be noted that pathological examination with light microscopy showed only limited beneficial effect of melatonin