The use of mini-organ cultures of human upper aerodigestive tract epithelia in ecogenotoxicology

Kleinsasser, Norbert; Juchhoff, Jutta; Wallner, Barbara C.; Bergner, Albrecht; Harréus, Ulrich; Gamarra, Fernando; Bührlen, Michael; Huber, Rudolf M.; Rettenmeier, Albert W.

doi:10.1016/j.mrgentox.2004.03.013

Cited by 37 publications

(15 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The use of 2% DMSO as solvents for GV196771 and GV150526 may have had a small effect on the cilia beat frequency (CBF) of the nasal epithelial cells and hence on the nasal absorption of the drugs (14,15). However, it has been shown that DMSO showed no damaging effect of cell DNA in cultures of human nasal epithelial cells (16). In the present studies it is suggested that the effects of DMSO would have been negligible since very different absorption patterns were found for the two drugs dissolved in 2% DMSO.…”

Section: Discussionmentioning

confidence: 46%

Evaluation of Direct Transport Pathways of Glycine Receptor Antagonists and an Angiotensin Antagonist from the Nasal Cavity to the Central Nervous System in the Rat Model

et al. 2008

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 46%

Evaluation of Direct Transport Pathways of Glycine Receptor Antagonists and an Angiotensin Antagonist from the Nasal Cavity to the Central Nervous System in the Rat Model

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Significance compared to the control is indicated by asterisks (*P < 0.05). were shown to remain viable over a period of minimum two weeks and were used for the determination of genotoxicity by xenobiotics [Kleinsasser et al, 2004]. In the current investigation, DNA damage by repetitive exposure of nasal mucosa cells to ZnO-NPs was assessed to obtain more distinct information on cumulative genotoxic effects and potential repair mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Repetitive exposure to zinc oxide nanoparticles induces dna damage in human nasal mucosa mini organ cultures

Hackenberg

Zimmermann

Scherzed

et al. 2011

Environ and Mol Mutagen

View full text Add to dashboard Cite

Data on the toxicological properties of zinc oxide nanoparticles (ZnO-NPs) is incomplete. ZnO-NPs may enter humans via inhalation or ingestion. The aim of the current study was to evaluate ZnO-NP-induced genotoxicity in three-dimensional (3D) mini organ cultures (MOCs) of human nasal mucosa following repeated exposure to ZnO-NP and regeneration. Nasal MOCs of 10 patients and ZnO-NPs were cultivated for one week and then characterized by electron microscopy. Nasal MOCs were partially covered by ciliated epithelium after one week of cultivation. ZnO-NPs were distributed to the cytoplasm and the nucleus. MOCs were exposed once, twice, or three times to 0.1 or 5 μg/ml of ZnO-NPs for 1 hr per exposure and were then evaluated for cytotoxicity and genotoxicity. MOCs were cultivated for 24 hr after the triple ZnO-NP exposure to allow for regeneration. ZnO-NP exposure did not result in significant cytotoxicity or apoptosis, as determined by trypan blue exclusion and caspase-3 activity, respectively. A significant increase in DNA damage was detected following repetitive exposure compared to single exposure to ZnO-NPs at 5 μg/ml, but not 0.1 μg/ml ZnO-NPs. At both concentrations of ZnO-NP, DNA fragmentation increased after 24 hr of regeneration. In contrast, DNA damage which was induced by the positive control, methyl methanesulfonate, was significantly reduced after 24-hr regeneration. Thus, our results suggest that repetitive exposure to low concentrations of ZnO-NPs results in persistent or ongoing DNA damage.

show abstract

“…In this study we used mini-organ cultures (MOCs) of oropharyngeal mucosa because of several advantages compared with isolated mucosal cells, cell lines, or other in-vitro models. First, by using these three-dimensional, completely epithelialized tissue cubes, repeated incubation of mucosal cells is possible without too much cellular damage and loss of cellular material after repetitive medium renewal (centrifugation, resuspension in medium) and loss of cell material (Kleinsasser et al, 2004). Second, compared with cells in intact tissue, isolated cells may have a limited metabolic competence, both for endogenous compounds and xenobiotics, a possibly altered DNA sensitivity and impaired repair capacity (Teissier et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Epigallocatechin-3-gallate reduces DNA damage induced by benzo[a]pyrene diol epoxide and cigarette smoke condensate in human mucosa tissue cultures

Baumeister

Reiter

Kleinsasser

et al. 2009

European Journal of Cancer Prevention

View full text Add to dashboard Cite

Although epidemiological studies indicate cancer preventive effects of diets rich in fruit and vegetables, large clinical intervention studies conducted to evaluate dietary supplementation with micronutrients, mostly vitamins, showed disappointing results in large parts. In contrast, there is encouraging epidemiologic data indicating great chemopreventive potential of a large group of phytochemicals, namely polyphenols. This study shows the DNA protective effect epigallocatechin-3-gallate, a tea catechin, and one of the best-studied substances within this group, on carcinogen-induced DNA fragmentation in upper aerodigestive tract cells. Cell cultures from fresh oropharyngeal mucosa biopsies were preincubated with epigallocatechin-3-gallate in different concentrations before DNA damage was introduced with the metabolically activated carcinogen benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide or cigarette smoke condensate. Effects on resulting DNA fragmentation were measured using the alkaline single-cell microgel electrophoresis (comet assay). Epigallocatechin-3-gallate significantly reduced benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide-induced DNA damage by up to 51% (P<0.001). Fragmentation induced by cigarette smoke condensate could be lowered by 47% (P<0.001). Data suggest a cancer preventive potential of epigallocatechin-3-gallate as demonstrated on a subcellular level. An additional mechanism of tea catechin action is revealed by using a primary mucosa culture model.

show abstract

The use of mini-organ cultures of human upper aerodigestive tract epithelia in ecogenotoxicology

Cited by 37 publications

References 27 publications

Evaluation of Direct Transport Pathways of Glycine Receptor Antagonists and an Angiotensin Antagonist from the Nasal Cavity to the Central Nervous System in the Rat Model

Evaluation of Direct Transport Pathways of Glycine Receptor Antagonists and an Angiotensin Antagonist from the Nasal Cavity to the Central Nervous System in the Rat Model

Repetitive exposure to zinc oxide nanoparticles induces dna damage in human nasal mucosa mini organ cultures

Epigallocatechin-3-gallate reduces DNA damage induced by benzo[a]pyrene diol epoxide and cigarette smoke condensate in human mucosa tissue cultures

Contact Info

Product

Resources

About