Genotoxicity of nitroso compounds and sodium dichromate in a model combining organ cultures of human nasal epithelia and the comet assay.
Genotoxic effects of xenobiotics are a possible step in tumor initiation in the mucosa of the upper aerodigestive tract. Using the comet assay, detecting genotoxicity in human tissue has been restricted to single incubations in vitro, but in vivo most xenobiotics harm their target in a repetitive or chronic manner. Therefore, we propose a model, which provides repetitive incubations in human upper aerodigestive tract mucosa cultures. Samples of human inferior nasal turbinate mucosa (n = 25) were cultured according to a modified version of a technique originally described by Steinsvåg. On day 1 fresh samples and on days 7, 9 and 11 organ cultures were incubated with N-nitrosodiethylamine (NDEA), sodium dichromate (Na2Cr2O7) and N'-methyl-N-nitro-N-nitrosoguanidine (MNNG). Mucosa samples and organ cultures, respectively, underwent a modified comet assay on days 1, 7 and 11. Genotoxicity could be shown for NDEA, Na2Cr2O7 and MNNG on days 1, 7 and 11. Duration of tissue culture and repetitive incubations did not significantly influence the results for NDEA. Nevertheless, Na2Cr2O7 and MNNG caused higher genotoxic effects on cultures subjected to the comet assay on day 11. This model may help to assess genotoxic hazards posed by environmental pollutants that have a cumulative character in repetitive or chronic exposure in vivo.
Kleinsasser
N H
NH
Department of Otolaryngology, Head and Neck Surgery, Ludwig-Maximilian University, Munich, Germany. norbert.kleinsasser@hno.med.uni-muenchen.de
Gamarra
F
F
Bergner
A
A
Wallner
B C
BC
Harréus
U A
UA
Juchhoff
J
J
Kastenbauer
E R
ER
Huber
R M
RM
D000328:Adult; D002840:Chromates / Q000009:adverse effects*; D020552:Comet Assay / Q000379:methods*; D046508:Culture Techniques; D053938:DNA Fragmentation / Q000187:drug effects* / Q000235:genetics; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects* / Q000473:pathology*; D009603:Nitroso Compounds / Q000009:adverse effects*; D014420:Turbinates / Q000187:drug effects* / Q000473:pathology*; D015262:Xenobiotics / Q000009:adverse effects*
D002840:Chromates; D009603:Nitroso Compounds; D015262:Xenobiotics; C016104:sodium bichromate