Please use this identifier to cite or link to this item: http://dx.doi.org/10.25673/38320
Title: Role of carcinogens factors in epigenetic silencing of Rassf1a, DAPK, p16, MT1A genes in human lung
Author(s): Gheit, HendaLook up in the Integrated Authority File of the German National Library
Referee(s): Foth, HeidiLook up in the Integrated Authority File of the German National Library
Simm, Andreas
Grasl-Kraupp, Bettina
Granting Institution: Martin-Luther-Universität Halle-Wittenberg
Issue Date: 2021
Extent: 1 Online-Ressource (91 Seiten)
Type: HochschulschriftLook up in the Integrated Authority File of the German National Library
Type: Doctoral thesis
Exam Date: 2021-05-07
Language: English
URN: urn:nbn:de:gbv:3:4-1981185920-385631
Abstract: In der vorliegenden Arbeit haben wir zunächst die Häufigkeit von epigenetischen Inaktivierungen durch Methylierung bei den tumorassoziierten Genen (Rassf1a), (DAPK), (p16) und Metallothionein 1 A untersucht. Von 26 Lungenkrebspatienten wurden Proben mit (Methyl PCR) untersucht. Die Häufigkeit der DNA-Methylierung lag bei: 62% für Rassf1a, 46% für DAPK, 54% für p16 und 39% für MT1A. Daneben haben wir an Primärkulturen von normalen humanen Lungenzellen die Rolle einer Langzeitexposition (NHBEZ, PLZ) gegenüber den Tabakrauchkondensat und Cadmium (II). Cadmium (II) induziert die aberrante Methylierung von DAPK in PLZ (p = 0,019) und in NHBEZ (p = 0,097). CSC führte zu einer signifikanten Induktion von p16-Methylierung in PLC (p = 0,047) Die Ergebnisse zeigen, dass Zellkulturen als In-vitro-Modelle einen Beitrag zur Langzeituntersuchung der Wirkung verschiedener Umweltschadstoffe leisten können.
A total of 24 out of 26 samples (92%) taken from lung cancer patients displayed hypermethylation in at least one of the genes tested (Rassf1a, DAPK, p16 or (MTIA). Rassf1a methylation was detectable in 62% of the patients. A high methylation ratio of 69% was found for Rassf1a in tumor tissue. Methylation frequency of DAPK across tissue types was (46.2%). This study showed methylation of p16 in 54%. Methylation of MT1A was observed in (39%). Explants of (NHBEC) and (PLC) from samples of 12 lung cancer patients can be cultured over a time period of up to five generations. When NHBEC and PLC are exposed to CSC (10 mg/l) or Cd (II) (5µM) Cadmium (II) significantly induces aberrant methylation of DAPK in PLC (p = 0.019) and in NHBEC (p = 0.097). Long term exposure to CSC led to significant induction of p16-methylation in PLC (p = 0.047). Human lung cell cultures as in-vitro models enable a long term follow up in studies on the effects of environmental carcinogens
URI: https://opendata.uni-halle.de//handle/1981185920/38563
http://dx.doi.org/10.25673/38320
Open Access: Open access publication
License: In Copyright
Appears in Collections:Interne-Einreichungen

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