Cytotoxicity and genotoxicity of versicolorins and 5-methoxysterigmatocystin in A549 cells

Jakšić, Daniela; Canlet, Cécile; Kopjar, Nevenka; Kosalec, Ivan; Klarić, Maja Šegvić

doi:10.1007/s00204-012-0871-x

Cited by 43 publications

(33 citation statements)

References 32 publications

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“…On the other hand, CTN caused minor MI and PRI inhibition, whereas OTA did not significantly affect cell progression neither exerted cytotoxic activity. Overall, these findings demonstrate STER toxicity at pM to μΜ concentrations on Hep3B cells, complying previous studies using different cytotoxicity assays, cell line models and concentrations around 0.5–6 × 10 −6 M [43]. Concerning CTN, the results obtained from in vitro studies for concentrations up to 10 −4 Μ support its cytotoxic tendency [44].…”

Section: Discussionsupporting

confidence: 89%

Mycotoxins’ Activity at Toxic and Sub-Toxic Concentrations: Differential Cytotoxic and Genotoxic Effects of Single and Combined Administration of Sterigmatocystin, Ochratoxin A and Citrinin on the Hepatocellular Cancer Cell Line Hep3B

Anninou

Chatzaki

Papachristou

et al. 2014

IJERPH

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Food safety organizations indicate the likelihood of constant human and animal exposure to mycotoxin mixtures as a possible negative public health impact. Risk assessment demonstrates that certain mycotoxins of Aspergillus and Penicillium spp. are toxic and hold a significant genotoxic efficacy at nanomolar concentrations. The aim of the current study was to investigate the potential cytogenetic effects of sterigmatocystin (STER), ochratoxin A (OTA) and citrinin (CTN) alone or in combination, at pM to μΜ concentrations, on the human hepatocellular cancer cell line Hep3B. MTT reduction, mitotic divisions, cell cycle delays and sister chromatid exchange rates (SCE) were determined as endpoints of metabolic activity, cytotoxicity, cytostaticity, and genotoxicity, respectively. All mycotoxin treatments induce SCE rates from 10−12 M, while their cytotoxic and cytostatic potential varies. In PRI and MI assays, but not at MTT, STER alone or in combination with OTA + CTN appeared cytostatic and cytotoxic, even at 10−12 M, while CTN alone and all other combinations displayed substantial cellular survival inhibition in doses ≥ 10−8 M. Co-administration of STER + OTA or STER + CTN in concentrations ≤ 10−1 M, increased the MI and MTT activity, while it did not affect the PRI. Mycotoxin co-treatments revealed in general similar-to-additive or antagonistic genotoxic and cytotoxic effects. Our results for the first time describe that STER alone or in combination with OTA and/or CTN share a cytotoxic and cytogenetic potential even at picoMolar concentrations on human hepatoma cells in vitro.

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Section: Discussionsupporting

confidence: 89%

Mycotoxins’ Activity at Toxic and Sub-Toxic Concentrations: Differential Cytotoxic and Genotoxic Effects of Single and Combined Administration of Sterigmatocystin, Ochratoxin A and Citrinin on the Hepatocellular Cancer Cell Line Hep3B

Anninou

Chatzaki

Papachristou

et al. 2014

IJERPH

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“…Sterigmatocystin has been shown to be genotoxic in vitro comparable to the aflatoxins, but seems to be significantly less hepatocarcinogenic [41]. Since a specific maximum limit for this toxin is lacking, the levels should be assessed with reference to the maximum limit of 2.0 µg/kg for aflatoxin B 1 .…”

Section: Resultsmentioning

confidence: 99%

Faces of a Changing Climate: Semi-Quantitative Multi-Mycotoxin Analysis of Grain Grown in Exceptional Climatic Conditions in Norway

Uhlig

Eriksen

Hofgaard³

et al. 2013

Toxins

126

112

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Recent climatological research predicts a significantly wetter climate in Southern Norway as a result of global warming. Thus, the country has already experienced unusually wet summer seasons in the last three years (2010–2012). The aim of this pilot study was to apply an existing multi-analyte LC-MS/MS method for the semi-quantitative determination of 320 fungal and bacterial metabolites in Norwegian cereal grain samples from the 2011 growing season. Such knowledge could provide important information for future survey and research programmes in Norway. The method includes all regulated and well-known mycotoxins such as aflatoxins, trichothecenes, ochratoxin A, fumonisins and zearalenone. In addition, a wide range of less studied compounds are included in the method, e.g., Alternaria toxins, ergot alkaloids and other metabolites produced by fungal species within Fusarium, Penicillium and Aspergillus. Altogether, 46 metabolites, all of fungal origin, were detected in the 76 barley, oats and wheat samples. The analyses confirmed the high prevalence and relatively high concentrations of type-A and -B trichothecenes (e.g., deoxynivalenol up to 7230 µg/kg, HT-2 toxin up to 333 µg/kg). Zearalenone was also among the major mycotoxins detected (maximum concentration 1670 µg/kg). Notably, several other Fusarium metabolites such as culmorin, 2-amino-14,16-dimethyloctadecan-3-ol and avenacein Y were co-occurring. Furthermore, the most prevalent Alternaria toxin was alternariol with a maximum concentration of 449 µg/kg. A number of Penicillium and Aspergillus metabolites were also detected in the samples, e.g., sterigmatocystin in concentrations up to 20 µg/kg.

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“…This may be explained by the presence of less polar metabolites next to STC, which might have antagonised STC cytotoxic activity. We can only speculate that this metabolite could be 5-metoxy-STC, which is structurally similar to STC and has much lower cytotoxic potency towards A549 cells than STC (Jakšić et al, 2012). However, a chromatogram of A. venenatus also showed the presence of less polar metabolites, but in lower concentration considering the peak area.…”

Section: Cytotoxic Potency Of Stc and Stc-producing Aspergilli -Possimentioning

confidence: 85%

“…Apart from STC, we also detected sharp peak of a less polar metabolite eluted right before STC in A. jensenii and A. venenatus chromatograms. We did not perform LC/MS/MS analyses and taking into account STC-derived metabolites and/or precursors we can only speculate that this metabolite might be 5-methoxy-STC (Jakšić et al, 2012). That peak is also comparable to 5-methoxy-STC detected by HPLC-DAD and TLC with AlCl 3 staining, in each of the five isolates of A. versicolor artificially inoculated on pine wood, wallpaper, gypsum board and chipboard (Nielsen et al, 1998).…”

Section: Stc-producing Ability Of Aspergilli (Section Versicolores)mentioning

confidence: 94%

See 1 more Smart Citation

Species diversity and cytotoxic potency of airborne sterigmatocystin-producing Aspergilli from the section Versicolores

Despot

Kocsubé

Bencsik

et al. 2016

Science of The Total Environment

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Cytotoxicity and genotoxicity of versicolorins and 5-methoxysterigmatocystin in A549 cells

Cited by 43 publications

References 32 publications

Mycotoxins’ Activity at Toxic and Sub-Toxic Concentrations: Differential Cytotoxic and Genotoxic Effects of Single and Combined Administration of Sterigmatocystin, Ochratoxin A and Citrinin on the Hepatocellular Cancer Cell Line Hep3B

Mycotoxins’ Activity at Toxic and Sub-Toxic Concentrations: Differential Cytotoxic and Genotoxic Effects of Single and Combined Administration of Sterigmatocystin, Ochratoxin A and Citrinin on the Hepatocellular Cancer Cell Line Hep3B

Faces of a Changing Climate: Semi-Quantitative Multi-Mycotoxin Analysis of Grain Grown in Exceptional Climatic Conditions in Norway

Species diversity and cytotoxic potency of airborne sterigmatocystin-producing Aspergilli from the section Versicolores

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