prikaz prve stranice dokumenta Genotoksični učinak aflatoksina B1, okratoksina A i sterigmatocistina na ljudske keratinocite
  Download
PDF 1.02 MB
master's thesis
Genotoksični učinak aflatoksina B1, okratoksina A i sterigmatocistina na ljudske keratinocite
Zagreb: University of Zagreb, Faculty of Pharmacy and Biochemistry, 2015. urn:nbn:hr:163:199771
Mužinić, Vedran
University of Zagreb
Faculty of Pharmacy and Biochemistry
Department of microbiology

Institutional repository: Repository of Faculty of Pharmacy and Biochemistry University of Zagreb

Cite this document

Mužinić, V. (2015). Genotoksični učinak aflatoksina B1, okratoksina A i sterigmatocistina na ljudske keratinocite (Master's thesis). Zagreb: University of Zagreb, Faculty of Pharmacy and Biochemistry. Retrieved from https://urn.nsk.hr/urn:nbn:hr:163:199771

Mužinić, Vedran. "Genotoksični učinak aflatoksina B1, okratoksina A i sterigmatocistina na ljudske keratinocite." Master's thesis, University of Zagreb, Faculty of Pharmacy and Biochemistry, 2015. https://urn.nsk.hr/urn:nbn:hr:163:199771

Mužinić, Vedran. "Genotoksični učinak aflatoksina B1, okratoksina A i sterigmatocistina na ljudske keratinocite." Master's thesis, University of Zagreb, Faculty of Pharmacy and Biochemistry, 2015. https://urn.nsk.hr/urn:nbn:hr:163:199771

Mužinić, V. (2015). 'Genotoksični učinak aflatoksina B1, okratoksina A i sterigmatocistina na ljudske keratinocite', Master's thesis, University of Zagreb, Faculty of Pharmacy and Biochemistry, accessed 25 November 2024, https://urn.nsk.hr/urn:nbn:hr:163:199771

Mužinić V. Genotoksični učinak aflatoksina B1, okratoksina A i sterigmatocistina na ljudske keratinocite [Master's thesis]. Zagreb: University of Zagreb, Faculty of Pharmacy and Biochemistry; 2015 [cited 2024 November 25] Available at: https://urn.nsk.hr/urn:nbn:hr:163:199771

V. Mužinić, "Genotoksični učinak aflatoksina B1, okratoksina A i sterigmatocistina na ljudske keratinocite", Master's thesis, University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, 2015. Available at: https://urn.nsk.hr/urn:nbn:hr:163:199771

Metadata
TitleGenotoksični učinak aflatoksina B1, okratoksina A i sterigmatocistina na ljudske keratinocite
Title (english)Genotoxic effect of aflatoxin B1, ochratoxin A and sterigmatocystin on human keratinocytes
AuthorVedran Mužinić
MentorMaja Šegvić Klarić (mentor)
Committee memberMaja Šegvić Klarić
Committee memberSanja Dabelić
GranterUniversity of Zagreb
Faculty of Pharmacy and Biochemistry
(Department of microbiology)
Zagreb
Defense date and country2015-07-08, Croatia
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Pharmacy
Pharmacy
Abstract
Ljudska koža najveći je organ ljudskog tijela, a kao takva je izložena brojnim potencijalno štetnim kemikalijama iz okoline. Mikotoksini aflatoksin B1 (AFB1), okratoksin A (OTA) i sterigmatocistin (STC) su produkti sekundarnog metabolizma filamentoznih plijesni različitih rodova (najčešće Aspergillus), a pri dugotrajnom izlaganju predstavljaju rizične čimbenike za razvoj hepatocelularnog i karcinoma bubrega. Njihova akutna i kronična toksičnost uglavnom je istraživana kroz unos hranom (zbog kontaminacije hrane suspektnim plijesnima) i inhalacijom (zbog mogućnosti udisanja spora plijesni pri profesionalnoj izloženosti), no još ne postoji mnogo istraživanja usredotočenih na perkutani unos toksina, kao i na njihove moguće kutane toksične učinke. Stoga je cilj ovoga rada bio istražiti genotoksični učinak navedenih mikotoksina na HaCaT stanice kao modelni sustav humanih epidermalnih keratinocita. Stanice su tretirane toksinima pojedinačno i u binarnim kombinacijama, sa koncentracijama toksina od po 1 i 10 μM, nakon čega je genotoksični potencijal mikotoksina određen kometnim testom u alkalnim uvjetima. Rezultati su pokazali da svi toksini značajno fragmentiraju DNA pri pojedinačnoj primjeni i primjeni u kombinacijama. Kombinacije toksina uglavnom pokazuju značajne razlike u odnosu na pojedinačno primjenjene toksine. Zaključujemo da svi navedeni toksini djeluju genotoksično na HaCaT stanice primjenjeni pojedinačno i u kombinacijama. STC pojedinačno pokazuje najveći genotoksični učinak. Kombinacija AFB1 i OTA pokazuje aditivno djelovanje, kombinacija OTA i STC pokazuje antagonistički učinak, a kombinacija AFB1 i STC pokazuje aditivno ili antagonističko djelovanje ovisno o koncentraciji AFB1. Ovi bi se nalazi mogli objasniti kompeticijom toksina na CYP450 enzime. Ujedno je ovaj rad prvi primjer ispitivanja genotoksičnosti kombinacije OTA i STC čiji se mehanizam djelovanja tek treba objasniti.
Abstract (english)
Human skin is the largest organ of a human body, commonly exposed to potentially harmful environmental chemicals. The mycotoxins aflatoxin B1, ochratoxin A and sterigmatocystin are produced by filamentous funghi of various genera (most commonly Aspergillus), and present risk factors for the development of hepatocellular and renal carcinoma during prolonged exposure. The acute and chronic toxicity of these toxins have most usually been studied through dietary (because of food contamination by suspect funghi) and inhalatory intake (because of a possibility of inhaling the spores during professional exposure). However, percutaneous intake, as well as possible cutaneous toxic effects of Aspergillus mycotoxins have been poorly investigated. The aim of this study was to investigate the toxin's genotoxic effect on HaCaT cells as a model system for human epidermal keratinocytes. The cells were tretated with toxins individually and in binary combinations, at concentrations of 1 and 10 μM, and genotoxic effect were determined by alkaline comet assay. The results have shown all toxins significantly fragment the DNA both individually and in combinations. The combinations usually show significant difference against the individually applied toxins. We conclude that all toxins exert genotoxicity upon the HaCaT cells at individual and combinatory application. Single STC showed the highest genotoxic effect, comparing to AFB1 and OTA. The combination of AFB1 and OTA showed an additive effect, the combination of OTA and STC exerted an antagonistic effect, and the combination of AFB1 and STC showed both the additive and antagonistic effect depending on concentration of AFB1. These findings could be explained by competitive binding of the toxins to the CYP450 enzymes. To our knowledge this is the firts reporton genotoxicity of the combination of OTA and STC, whose mechanism has yet to be explained.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:163:199771
Study programmeTitle: Pharmacy
Study programme type: university
Study level: integrated undergraduate and graduate
Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
Type of resourceText
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2016-01-19 11:28:53