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Dr. Jakšić Daniela
University of Zagreb, Faculty of Pharmacy and Biochemistry

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0 Microbiology
0 Mycology
0 Mycotoxins
0 Pharmacy
0 Aspergillus

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Journal article
Published: 30 June 2021 in Toxins
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Sterigmatocystin (STC) and 5-methoxysterigmatocystin (5-M-STC) are structurally related mycotoxins with cytotoxic and genotoxic properties. In the present study, we hypothesized that DNA damage induced by non-cytotoxic concentrations of single and combined mycotoxins could alter the phosphorylation of the checkpoint proteins Chk2 and FANCD2 (ELISA) in HepG2 and A549 cells. The cytotoxic potential (MTT test) of single and combined STC and 5-M-STC, the nature of their interaction (additivity, antagonism, or synergy) and DNA damage level (alkaline comet assay) in HepG2 and A549 cells were also investigated. All experiments were performed after 24 h of mycotoxin treatment. 5-M-STC was 10-folds more cytotoxic than STC to both HepG2 and A549 cells. Both mycotoxins are genotoxic to HepG2 and A549 cells by inducing both double and single DNA strand breaks that activate Chk2 (especially in HepG2 cells) but not the FANCD2 protein. STC exerted higher genotoxic potential than 5-M-STC in HepG2 and A549 cells when both toxins were applied individually at the same concentration. Dual combinations of non-cytotoxic mycotoxin concentrations showed additive to antagonizing cytotoxic and genotoxic effects. The absence and low activation of checkpoint proteins during prolonged exposure to non-cytotoxic concentrations of STC and 5-M-STC could support cell proliferation and carcinogenesis.

ACS Style

Sanja Dabelić; Domagoj Kifer; Daniela Jakšić; Nevenka Kopjar; Maja Klarić. Sterigmatocystin, 5-Methoxysterigmatocistin, and Their Combinations are Cytotoxic and Genotoxic to A549 and HepG2 Cells and Provoke Phosphorylation of Chk2, but not FANCD2 Checkpoint Proteins. Toxins 2021, 13, 464 .

AMA Style

Sanja Dabelić, Domagoj Kifer, Daniela Jakšić, Nevenka Kopjar, Maja Klarić. Sterigmatocystin, 5-Methoxysterigmatocistin, and Their Combinations are Cytotoxic and Genotoxic to A549 and HepG2 Cells and Provoke Phosphorylation of Chk2, but not FANCD2 Checkpoint Proteins. Toxins. 2021; 13 (7):464.

Chicago/Turabian Style

Sanja Dabelić; Domagoj Kifer; Daniela Jakšić; Nevenka Kopjar; Maja Klarić. 2021. "Sterigmatocystin, 5-Methoxysterigmatocistin, and Their Combinations are Cytotoxic and Genotoxic to A549 and HepG2 Cells and Provoke Phosphorylation of Chk2, but not FANCD2 Checkpoint Proteins." Toxins 13, no. 7: 464.

Journal article
Published: 23 November 2020 in Toxins
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Sterigmatocystin (STC) and 5-methoxysterigmatocystin (5-M-STC) are mycotoxins produced by common damp indoor Aspergilli series Versicolores. Since both STC and 5-M-STC were found in the dust of indoor occupational and living areas, their occupants may be exposed to these mycotoxins, primarily by inhalation. Thus, STC and 5-M-STC were intratracheally instilled in male Wistar rats using doses (0.3 mg STC/kg of lung weight (l.w.); 3.6 mg 5-M-STC/kg l.w.; toxin combination 0.3 + 3.6 mg/kg l.w.) that corresponded to concentrations detected in the dust of damp indoor areas in order to explore cytotoxicity, vascular permeability, immunomodulation and genotoxicity. Single mycotoxins and their combinations insignificantly altered lactate-dehydrogenase activity, albumin, interleukin-6, tumor necrosis factor-α and chemokine macrophage inflammatory protein-1α concentrations, as measured by ELISA in bronchioalveolar lavage fluid upon 24 h of treatment. In an alkaline comet assay, both mycotoxins provoked a similar intensity of DNA damage in rat lungs, while in a neutral comet assay, only 5-M-STC evoked significant DNA damage. Hence, naturally occurring concentrations of individual STC may induce DNA damage in rat lungs, in which single DNA strand breaks prevail, while 5-M-STC was more responsible for double-strand breaks. In both versions of the comet assay treatment with STC + 5-M-STC, less DNA damage intensity occurred compared to single mycotoxin treatment, suggesting an antagonistic genotoxic action.

ACS Style

Daniela Jakšić; Ida Ćurtović; Domagoj Kifer; Dubravka Rašić; Nevenka Kopjar; Vedran Micek; Maja Peraica; Maja Šegvić Klarić. Single-Dose Toxicity of Individual and Combined Sterigmatocystin and 5-Methoxysterigmatocistin in Rat Lungs. Toxins 2020, 12, 734 .

AMA Style

Daniela Jakšić, Ida Ćurtović, Domagoj Kifer, Dubravka Rašić, Nevenka Kopjar, Vedran Micek, Maja Peraica, Maja Šegvić Klarić. Single-Dose Toxicity of Individual and Combined Sterigmatocystin and 5-Methoxysterigmatocistin in Rat Lungs. Toxins. 2020; 12 (11):734.

Chicago/Turabian Style

Daniela Jakšić; Ida Ćurtović; Domagoj Kifer; Dubravka Rašić; Nevenka Kopjar; Vedran Micek; Maja Peraica; Maja Šegvić Klarić. 2020. "Single-Dose Toxicity of Individual and Combined Sterigmatocystin and 5-Methoxysterigmatocistin in Rat Lungs." Toxins 12, no. 11: 734.

Journal article
Published: 12 November 2020 in Journal of Fungi
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Mycotoxin-producing Aspergilli (Circumdati, Flavi, and Nigri), usually associated with contaminated food, may also cause respiratory disorders and are insufficiently studied in water-damaged indoor environments. Airborne (N = 71) and dust borne (N = 76) Aspergilli collected at post-flood and control locations in Croatia resulted in eleven different species based on their calmodulin marker: A. ochraceus, A. ostianus, A. pallidofulvus, A. sclerotiorum, and A. westerdijkiae (Circumdati); A. flavus (Flavi); and A. tubingensis, A. welwitschiae, A. niger, A. piperis, and A. uvarum (Nigri). Most of the airborne (73%) and dust borne (54%) isolates were found at post-flood locations, and the highest concentrations measured in indoor air (5720 colony-forming units (CFU)/m3) and dust (2.5 × 105 CFU/g) were up to twenty times higher than in the control locations. A. flavus dominated among airborne isolates (25%) at the unrepaired locations, while 56% of the dust borne Aspergilli were identified as A. tubingensis and A. welwitschiae. The ability of identified isolates to produce mycotoxins aflatoxin B1 (AFB1), fumonisin B2 (FB2), and ochratoxin A were assessed by LC-MS analysis. All ochratoxin A (OTA)-producing Circumdati belonged to A. westerdijkiae (13.7 ± 15.81 µg/mL); in the section, FlaviA. flavus produced AFB1 (2.51 ± 5.31 µg/mL), while A. welwitschiae and A. niger (section Nigri) produced FB2 (6.76 ± 13.51 µg/mL and 11.24 ± 18.30 µg/mL, respectively). Water damage dominantly supported the occurrence of aflatoxigenic A. flavus in indoor environments. Yet unresolved, the causal relationship of exposure to indoor Aspergilli and adverse health effects may support the significance of this research.

ACS Style

Daniela Jakšić; Miranda Sertić; Sándor Kocsubé; Ivana Kovačević; Domagoj Kifer; Ana Mornar; Biljana Nigović; Maja Šegvić Klarić. Post-Flood Impacts on Occurrence and Distribution of Mycotoxin-Producing Aspergilli from the Sections Circumdati, Flavi, and Nigri in Indoor Environment. Journal of Fungi 2020, 6, 282 .

AMA Style

Daniela Jakšić, Miranda Sertić, Sándor Kocsubé, Ivana Kovačević, Domagoj Kifer, Ana Mornar, Biljana Nigović, Maja Šegvić Klarić. Post-Flood Impacts on Occurrence and Distribution of Mycotoxin-Producing Aspergilli from the Sections Circumdati, Flavi, and Nigri in Indoor Environment. Journal of Fungi. 2020; 6 (4):282.

Chicago/Turabian Style

Daniela Jakšić; Miranda Sertić; Sándor Kocsubé; Ivana Kovačević; Domagoj Kifer; Ana Mornar; Biljana Nigović; Maja Šegvić Klarić. 2020. "Post-Flood Impacts on Occurrence and Distribution of Mycotoxin-Producing Aspergilli from the Sections Circumdati, Flavi, and Nigri in Indoor Environment." Journal of Fungi 6, no. 4: 282.

Review
Published: 27 October 2020 in International Journal of Environmental Research and Public Health
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Crops contaminated by aflatoxins (AFs), the toxic and carcinogenic mycotoxins produced namely by Aspergillus flavus and Aspergillus parasiticus, have severe impacts on human health. Changes in temperature and water availability related to actual climate changes (increased temperature, heavy rainfalls, and droughts) are modulating factors of mould growth and production of mycotoxins. To protect human and animal health from the harmful effects caused by AFs, the development of a safe and effective multifaceted approach in combating food and feed contamination with AFs is necessary. This review aims to collect and analyze the available information regarding AF presence in food and feed to reinforce AF management and to prevent health issues related to the AF exposure in the light of actual climate changes.

ACS Style

Rafael Valencia-Quintana; Mirta Milić; Daniela Jakšić; Maja Šegvić Klarić; María Tenorio-Arvide; Guillermo Pérez-Flores; Stefano Bonassi; Juana Sánchez-Alarcón. Environment Changes, Aflatoxins, and Health Issues, a Review. International Journal of Environmental Research and Public Health 2020, 17, 7850 .

AMA Style

Rafael Valencia-Quintana, Mirta Milić, Daniela Jakšić, Maja Šegvić Klarić, María Tenorio-Arvide, Guillermo Pérez-Flores, Stefano Bonassi, Juana Sánchez-Alarcón. Environment Changes, Aflatoxins, and Health Issues, a Review. International Journal of Environmental Research and Public Health. 2020; 17 (21):7850.

Chicago/Turabian Style

Rafael Valencia-Quintana; Mirta Milić; Daniela Jakšić; Maja Šegvić Klarić; María Tenorio-Arvide; Guillermo Pérez-Flores; Stefano Bonassi; Juana Sánchez-Alarcón. 2020. "Environment Changes, Aflatoxins, and Health Issues, a Review." International Journal of Environmental Research and Public Health 17, no. 21: 7850.

Review
Published: 29 February 2020 in Toxins
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In the past decades, many studies have examined the nature of the interaction between mycotoxins in biological models classifying interaction effects as antagonisms, additive effects, or synergisms based on a comparison of the observed effect with the expected effect of combination. Among several described mathematical models, the arithmetic definition of additivity and factorial analysis of variance were the most commonly used in mycotoxicology. These models are incorrectly based on the assumption that mycotoxin dose-effect curves are linear. More appropriate mathematical models for assessing mycotoxin interactions include Bliss independence, Loewe’s additivity law, combination index, and isobologram analysis, Chou-Talalays median-effect approach, response surface, code for the identification of synergism numerically efficient (CISNE) and MixLow method. However, it seems that neither model is ideal. This review discusses the advantages and disadvantages of these mathematical models.

ACS Style

Domagoj Kifer; Daniela Jakšić; Maja Šegvić Klarić. Assessing the Effect of Mycotoxin Combinations: Which Mathematical Model Is (the Most) Appropriate? Toxins 2020, 12, 153 .

AMA Style

Domagoj Kifer, Daniela Jakšić, Maja Šegvić Klarić. Assessing the Effect of Mycotoxin Combinations: Which Mathematical Model Is (the Most) Appropriate? Toxins. 2020; 12 (3):153.

Chicago/Turabian Style

Domagoj Kifer; Daniela Jakšić; Maja Šegvić Klarić. 2020. "Assessing the Effect of Mycotoxin Combinations: Which Mathematical Model Is (the Most) Appropriate?" Toxins 12, no. 3: 153.

Journal article
Published: 06 November 2019 in Marine Drugs
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We demonstrated the hitherto unknown property of the mycotoxin sterigmatocystin (STC) to provide homogeneous solutions in aqueous medium by forming a unique aggregate type (not formed by analogous aflatoxins), characterized by exceptionally strong circular dichroism (CD) bands in the 300–400 nm range. Results showed that these CD bands do not originate from intrinsic STC chirality but are a specific property of a peculiar aggregation process similar to psi-DNA CD response. Transmission electron microscopy (TEM) experiments revealed a fine fiber network resembling a supramolecular gel structure with helical fibers. Thermodynamic studies of aggregates by differential scanning calorimetry (DSC) revealed high reversibility of the dominant aggregation process. We demonstrated that the novel STC psi-CD band at 345 nm could be applied at biorelevant conditions (100 nanomolar concentration) and even in marine-salt content conditions for specific and quantitative monitoring of STC. Also, we showed that STC strongly non-covalently interacts with ds-DNA with likely toxic effects, thus contrary to the previous belief requiring prior enzyme epoxidation.

ACS Style

Daniela Jakšić; Maja Šegvić Klarić; Ivo Crnolatac; Nataša Šijaković Vujičić; Vilko Smrečki; Marcin Górecki; Gennaro Pescitelli; Ivo Piantanida. Unique Aggregation of Sterigmatocystin in Water Yields Strong and Specific Circular Dichroism Response Allowing Highly Sensitive and Selective Monitoring of Bio-Relevant Interactions. Marine Drugs 2019, 17, 629 .

AMA Style

Daniela Jakšić, Maja Šegvić Klarić, Ivo Crnolatac, Nataša Šijaković Vujičić, Vilko Smrečki, Marcin Górecki, Gennaro Pescitelli, Ivo Piantanida. Unique Aggregation of Sterigmatocystin in Water Yields Strong and Specific Circular Dichroism Response Allowing Highly Sensitive and Selective Monitoring of Bio-Relevant Interactions. Marine Drugs. 2019; 17 (11):629.

Chicago/Turabian Style

Daniela Jakšić; Maja Šegvić Klarić; Ivo Crnolatac; Nataša Šijaković Vujičić; Vilko Smrečki; Marcin Górecki; Gennaro Pescitelli; Ivo Piantanida. 2019. "Unique Aggregation of Sterigmatocystin in Water Yields Strong and Specific Circular Dichroism Response Allowing Highly Sensitive and Selective Monitoring of Bio-Relevant Interactions." Marine Drugs 17, no. 11: 629.