Genotoxicity of Nitroso Compounds and Sodium Dichromate in a Model Combining Organ Cultures of Human Nasal Epithelia and the Comet Assay

Kleinsasser, Norbert; Gamarra, Fernando; Bergner, Albrecht; Wallner, Barbara C.; Harréus, Ulrich; Juchhoff, Jutta; Kastenbauer, E.; Huber, Rudolf M.

doi:10.1159/000055730

Cited by 24 publications

(12 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Since the three-dimensional (3D) architecture of the tissue of origin is lost in these culture conditions, some authors prefer using different organ culture methods to simulate the in vivo situation in a superior way [Bals et al, 1998]. Inspired by techniques creating organ cultures from adenoid tissue [Steinsvåg et al, 1991], 3D nasal mucosa MOCs, which were derived from human inferior turbinate tissue samples, were established [Kleinsasser et al, 2001]. Epithelial cells on the surface of nasal mucosa MOCs Environmental and Molecular Mutagenesis.…”

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

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

show abstract

“…For judging the results, MNNG, which is well known as a carcinogenic substance in humans [7], was chosen as a positive control agent. This allowed classification of the amount of genotoxic dam- …”

Section: Positive Controlmentioning

confidence: 99%

Genotoxicity studies on permethrin, DEET and diazinon in primary human nasal mucosal cells

Tisch¹,

Schmezer

Faulde³

et al. 2002

European Archives of Oto-Rhino-Laryngology

View full text Add to dashboard Cite

Possible genotoxic effects exerted by three widely used pesticides, permethrin, N,N-diethyl-m-toluamide (DEET) and diazinon, in primary human nasal mucosal cells were investigated. Primary nasal mucosa cells were prepared from tissue biopsies taken from 21 patients who underwent nasal surgery. Cells were exposed to 0.5-1.0 mM concentrations of permethrin, DEET and diazinon for 60 min. Genotoxic effects were detected by the alkaline microgel electrophoresis assay ("comet assay"). Within the concentration range, no significant cytotoxic effects were observed, but all three tested pesticides showed a significant genotoxic response that was concentration dependent. More pronounced genotoxic effects were observed in mucosal cells from the middle turbinate than in the inferior turbinate. The results provide some evidence for the potential carcinogenicity of these agents to human nasal mucosal cells. This should be further investigated.

show abstract

“…Furthermore, the chemical composition of potentially mutagenic saliva is dependent on toxification and detoxification metabolic pathways that are influenced by different polymorphisms (8,9). To what extent in vitro tests, like the plating efficiency index, illustrate carcinogenic phenomena in vivo remains controversial (26). However, it is beyond controversy that such in vitro techniques can help in understanding the stepwise malignant transformation of healthy tissue.…”

Section: Discussionmentioning

confidence: 99%

Saliva as a biomarker for head and neck squamous cell carcinoma: In vitro detection of cytotoxic effects by using the plating efficiency index

Bloching¹,

Barnes²,

Aust³

et al. 2007

Oncol Rep

View full text Add to dashboard Cite

Abstract. Worldwide, the incidence of head and neck squamous cell carcinoma (HNSCC) is increasing. The development of an effective prevention program would provide a promising opportunity to control this disease. We applied the 'plating efficiency index' of Chinese hamster lung fibroblasts to demonstrate the presence of cytotoxic effects in saliva samples from cancer patients as well as from healthy probands. Correlations between individual risk factors and the cytotoxic effects of saliva specimens were analysed and evaluated. Saliva samples were obtained from male patients (n=43) with carcinomas of the upper aerodigestive tract, and from a healthy age-matched male control group (n=131) with different tobacco and alcohol consumption habits. The extraction of non-stimulated sober saliva was chosen for this investigation. In vitro cytotoxicity of the saliva was detected using the permanent mammalian cell line V79 (lung fibroblasts) of Chinese hamsters. The determination of the plating efficiency index was made in the logarithmic growth phase of the initial cell culture. A reduction in cell colonies (plating efficiency) of at least 50% was defined as strongly cytotoxic. A significant direct correlation was found between daily tobacco consumption and the reduction of plating efficiency (p<0.0001). We found only a moderate increase in the cytotoxicity of tested saliva samples in correlation with daily alcohol uptake. The difference between tumor patients and healthy probands was highly significant (χ 2 test; p=0.001). Using the method of logistic regression analysis, we found a 3.6-fold increased cancer risk in probands with cytotoxic saliva (p<0.001). According to our results, the plating efficiency index seems to be a suitable method for the detection of increased cancer risk. In combination with several effective biomarkers on cytogenetic end-points, it may help to establish biomonitoring programs for secondary cancer prevention. IntroductionPrimary cancers of the head and neck region have varying types of histology. Squamous cell carcinomas (SCCs) are among the most common malignancies of the upper aerodigestive tract (1). The incidence of these tumors varies worldwide on the basis of changing 'lifestyle' factors (2,3) such as chronic tobacco and alcohol consumption or changing exposure to environmental carcinogens. Despite multimodal therapies with often mutilating surgical procedures (especially in extended tumor stages), the prognosis for these tumors remains poor. Hence, the development of effective prevention programs would provide a promising opportunity to control this increasingly common disease.In general, there are two different methods of disease prevention. First, and most effective, is the reduction of avoidable exogenous risk factors. The second involves the identification of people bearing individual increased cancer risk, which may help in the detection of early-stage carcinomas (4-7). Hopefully, this will be achieved in the future through the use of biomarkers showing biological effects, like per...

show abstract

Genotoxicity of Nitroso Compounds and Sodium Dichromate in a Model Combining Organ Cultures of Human Nasal Epithelia and the Comet Assay

Cited by 24 publications

References 21 publications

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

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

Genotoxicity studies on permethrin, DEET and diazinon in primary human nasal mucosal cells

Saliva as a biomarker for head and neck squamous cell carcinoma: In vitro detection of cytotoxic effects by using the plating efficiency index

Contact Info

Product

Resources

About