Genotoxic effects of myosmine in human lymphocytes and upper aerodigestive tract epithelial cells

Kleinsasser, Norbert; Wallner, Barbara C.; Harréus, Ulrich; Zwickenpflug, Wolfgang; Richter, Elmar

doi:10.1016/s0300-483x(03)00296-8

Cited by 47 publications

(22 citation statements)

References 20 publications

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“…De Zwart et al (28) reported that lipid peroxidation produced several toxic byproducts such as MDA, which can attack cellular targets including DNA, inducing mutagenicity and carcinogenicity. The increased MDA level after myosmine treatment, might also contribute to the mutagenic and genotoxic effects of myosmine (9,(29)(30)(31). Glutathione is required to maintain the normal reduced state of cells and to counteract the adverse effects of oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Effects of Myosmine on Antioxidative Defence in Rat Liver

Simeonova

Vitcheva

Gorneva

et al. 2012

Archives of Industrial Hygiene and Toxicology

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Myosmine [3-(1-pyrrolin-2-yl) pyridine] is an alkaloid structurally similar to nicotine, which is known to induce oxidative stress. In this study we investigated the effects of myosmine on enzymatic and nonenzymatic antioxidative defence in rat liver. Wistar rats received a single i.p. injection of 19 mg kg -1 of myosmine and an oral dose of 190 mg kg -1 by gavage. Nicotine was used as a positive control. Through either route of administration, myosmine altered the hepatic function by decreasing the levels of reduced glutathione, superoxide dismutase, and glutathione peroxidase activities on one hand and by increasing malondialdehyde, catalase, and glutathione reductase activity on the other. Compared to control, both routes caused signifi cant lipid peroxidation in the liver and altered hepatic enzymatic and non-enzymatic antioxidative defences. The pro-oxidant effects of myosmine were comparable with those of nicotine.

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Section: Discussionmentioning

confidence: 99%

Effects of Myosmine on Antioxidative Defence in Rat Liver

Simeonova

Vitcheva

Gorneva

et al. 2012

Archives of Industrial Hygiene and Toxicology

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“…The alkaline comet assay was carried out as described previously by Kleinsasser et al (2003). Briefly, after treatments with different concentrations of OTA (5, 10 and 20 μM), Het-1A cells were harvested and mixed with 0.75% low-melting point agarose (Bio Basic Inc., Amherst, NY, USA), then layered onto microscope slides pre-coated with normal-melting point agarose.…”

Section: Alkaline Comet Assaysmentioning

confidence: 99%

Ochratoxin A induces DNA damage and G2 phase arrest in human esophageal epithelium Het-1A cells <i>in vitro </i>

et al. 2015

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-Ochratoxin A (OTA), a toxin produced by several species of Aspergillus and Penicillium, is one of the most abundant food-contaminating mycotoxins. The International Agency for Research on Cancer (IARC) has classified OTA as a possible human carcinogen. Our previous study showed that there were high levels of OTA contaminations in wheat in the areas with high incidence of esophageal cancer in north China. This finding suggests that exposure to low levels of OTA may be a critical etiological factor for esophageal cancer in these areas. However, up to now, the potential biological effects of OTA on human esophageal epithelial cells have not been fully elucidated. In the present study, we explored the cytotoxicity of OTA in human esophageal epithelium immortalized cells (Het-1A). We found that OTA could induce DNA strand breaks and chromosome aberrations in Het-1A cells. OTA-induced DNA damage was followed by G2 cell cycle arrest, and down-regulation of Cdc2 and cyclinB1 contributed to the OTA-induced G2 arrest in Het-1A cells. Additionally, OTA induced apoptosis in Het-1A cells by activating caspase-3. In conclusion, our results indicated that OTA could induce DNA damage, G2 arrest and apoptosis in Het-1A cells, which may be involved in the esophageal toxicity of OTA.

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“…However, in the test system, Escherichia coli polA ϩ /pol Ϫ , a weak mutagenic response, was observed (Riebe et al, 1982). The mutagenic potential of myosmine was confirmed by the detection of DNA damage in human lymphocytes and nasal mucosa cells by the Comet assay (Kleinsasser et al, 2003). Under nitrosation conditions at pH 3 to 5, covalent binding of radioactivity derived from 3 H-myos-mine to calf thymus DNA was observed in vitro .…”

mentioning

confidence: 91%

Metabolism of Myosmine in Wistar Rats

Zwickenpflug

Tyroller²,

Richter³

2005

Drug Metab Dispos

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ABSTRACT:The alkaloid myosmine is present not only in tobacco products but also in various foods. Myosmine is easily nitrosated, yielding 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB) and the esophageal tobacco carcinogen N-nitrosonornicotine. Due to its widespread occurrence, investigations on the metabolism and activation of myosmine are needed for risk assessment. Therefore, the metabolism of myosmine has been studied in Wistar rats treated with single oral doses of [pyridine-5-3 H]myosmine at 0.001, 0.005, 0.5, and 50 mol/kg body weight. Oral administration was achieved by feeding a labeled apple bite. Radioactivity was completely recovered in urine and feces within 48 h. At the two lower doses, 0.001 and 0.005 mol/kg, a higher percentage of the radioactivity was excreted in urine (86.2 ؎ 4.9% and 88.9 ؎ 1.7%) as compared with the higher doses, 0.5 and 50 mol/kg, where only 77.8 ؎ 7.3% and 75.4 ؎ 6.6% of the dose was found in urine. Within 24 h, urinary excretion of radioactivity was nearly complete with less than 4% of the total urinary output appearing between 24 and 48 h. The two major metabolites accounting for >70% of total radioactivity in urine were identified as 3-pyridylacetic acid (20-26%) and 4-oxo-4-(3-pyridyl)butyric acid (keto acid, 50-63%) using UV-diode array detection and gas chromatography-mass spectrometry measurements. 3-Pyridylmethanol (3-5%), 3-hydroxymyosmine (2%) and HPB (1-3%) were detected as minor metabolites. 3-Hydroxymyosmine is exclusively formed from myosmine and therefore might be used as a urinary biomarker for myosmine exposure in the future.

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Genotoxic effects of myosmine in human lymphocytes and upper aerodigestive tract epithelial cells

Cited by 47 publications

References 20 publications

Effects of Myosmine on Antioxidative Defence in Rat Liver

Effects of Myosmine on Antioxidative Defence in Rat Liver

Ochratoxin A induces DNA damage and G2 phase arrest in human esophageal epithelium Het-1A cells <i>in vitro </i>

Metabolism of Myosmine in Wistar Rats

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