Ochratoxin A: induction of (oxidative) DNA damage, cytotoxicity and apoptosis in mammalian cell lines and primary cells

Kamp, Hennicke; Eisenbrand, Gerhard; Schlatter, Josef Rudolf; Würth, Kirsten; Janzowski, C.

doi:10.1016/j.tox.2004.08.004

Cited by 152 publications

(115 citation statements)

References 39 publications

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“…In vitro and in vivo data suggest an involvement of oxidative stress in OTA-mediated cytotoxicity [1,4,16,17,23,30]. In fact, we observed in kidney tubulus cells a significant increase in reactive oxygen species production after OTA treatment already at relatively low OTA concentrations (0.5-2.5 lmol/L) [5] which were similar to those concentrations we used in the present study in neurons.…”

Section: Discussionsupporting

confidence: 88%

Ochratoxin A induces apoptosis in neuronal cells

et al. 2009

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The mycotoxin ochratoxin A (OTA), which is produced by Aspergillus and Penicillium subspecies, is a frequently present contaminant of food and feedstuffs. OTA exhibits a wide range of toxic activities including nephro-and hepatotoxicity. However, little is known regarding potential neurotoxic effects of OTA. In the present study primary neurons as well as SH-SY5Y neuronal cells were incubated with increasing concentrations of OTA (0.1-2.5 lmol/L). OTA treatment resulted in a dose-dependent increase in cytotoxicity in both neuronal cell types. Caspase-9 and caspase-3 were activated in response to OTA treatment. Furthermore, caspase inhibitors were effective in partly counteracting OTA induced neurocytotoxicity. OTA induced apoptosis was accompanied by a loss of mitochondria membrane potential. Overall, present data indicated that OTA is neurotoxic at relatively low concentrations. OTA induced neurotoxicity seems to be, at least party, mediated by apoptosis. OTA may contribute to the pathogenesis of neurodegenerative diseases (e.g. Alzheimer's and Parkinson's disease) in which apoptotic processes are centrally involved.

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Section: Discussionsupporting

confidence: 88%

Ochratoxin A induces apoptosis in neuronal cells

et al. 2009

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“…Low GSH concentrations in vitro (Schaaf et al, 2002;Kamp et al, 2005b) and in vivo have been reported after exposure to OTA (Gautier et al, 2001;Meki and Hussein, 2001;Ozcelik et al, 2004), as well as decreases in the activities of CAT, GPx, GR, and SOD in both liver and kidney (Meki and Hussein, 2001;Ozcelik et al, 2004). Here, we found that chronic treatment with OTA tended to reduce SOD mRNA levels, suggesting that OTA affects SOD at the transcriptional level too.…”

Section: Oxidative Damage and Heat Shock Responsesupporting

confidence: 68%

Early cytotoxic effects of ochratoxin A in rat liver: A morphological, biochemical and molecular study

et al. 2006

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We characterized the overall early effect of chronic ochratoxin A (OTA) treatment on rat liver, analyzing different aspects related to: (i) fibrosis, by measuring collagen content and turnover, and ␣-smooth muscle actin (␣SMA); (ii) oxidative stress and stress response, by analyzing protein carbonylation, superoxide dismutase (SOD) and heat shock protein (HSP70) gene expression; (iii) the possible tumor promoter effect, evaluating cadherin and connexin (CX) mRNA levels. Light microscopy analysis showed no histological differences in OTA-treated and control (CT) rats. Collagen content, determined by computer analysis of Sirius redstained liver sections, was similar in both groups. In liver homogenates COL-I, COL-III, TIMP-1 and TGF-␤1 mRNA levels and ␣SMA were unaffected by OTA. Matrix metalloproteinase (MMP)-1, MMP-2 and MMP-9 protein levels were also similar in the two groups. Protein carbonylation, a marker of severe oxidative stress, was not evident in the homogenates of OTA-treated livers; superoxide dismutase (SOD) mRNA tended to be lower and HSP70 was strongly down-regulated. OTA reduced E-cadherin and DSC-2 transcription, and down-regulated liver CX26, CX32 and CX43. In conclusion, these in vivo results show that OTA-induced liver injury involves a reduction in the ability to counterbalance oxidative stress, maybe leading to altered gap junction intercellular communication and loss of cell adhesion and polarity. This suggests that mild oxidative damage might be a key factor, in combination with other cytotoxic effects, in triggering the promotion of liver tumors after exposure to OTA.

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“…Zearalenone could induce DNA adduct formation and chromosomal aberration in vivo and vitro (Pfohl-Leszkowicz et al, 1995;Thust et al, 1983;Galloway et al, 1987). Several studies also reported that OTA induced DNA strand breaks in cultured primary kidney cells from human, rat and Chinese hamster ovary fibroblast cell line AA8 (Robbiano et al, 2004;Kamp et al, 2005b;Cosimi et al, 2009). Recently, Kuroda found that OTA induced DNA strand breaks, deletion mutations, G2/M arrest and apoptosis in the kidney in rats and mice (Kuroda et al, 2014;Kuroda et al, 2015).…”

Section: Discussionmentioning

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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Ochratoxin A: induction of (oxidative) DNA damage, cytotoxicity and apoptosis in mammalian cell lines and primary cells

Cited by 152 publications

References 39 publications

Ochratoxin A induces apoptosis in neuronal cells

Ochratoxin A induces apoptosis in neuronal cells

Early cytotoxic effects of ochratoxin A in rat liver: A morphological, biochemical and molecular study

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

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