Genotoxic effects of pentachlorophenol, lindane, transfluthrin, cyfluthrin, and natural pyrethrum on human mucosal cells of the inferior and middle nasal conchae.
BACKGROUND
Animal experiments and epidemiological studies suggest that pentachlorophenol (PCP) and gamma-hexachlorocyclohexane (lindane) should be classified as possible human carcinogens. In the past, both have had a variety of applications in the civilian and military sectors and in forestry. They have, e.g., been used to impregnate and treat uniforms and other fabrics and to control human lice. Animal experiments indicate that PCP in particular causes mutations and chromosome aberrations and thus DNA damage. Studies on whether or not this also applies to newer substances and especially to natural type I and type II pyrethroids still are not available. What is particularly lacking are data on the genotoxic effects of these substances on human target cells. Our study describes the genotoxic effects of PCP, lindane, transfluthrin, cyfluthrin, and natural pyrethrum on human mucosal cells of the inferior and middle nasal conchae.


METHODS
Epithelial cells were isolated from nasal mucosa, which was removed in the surgical treatment of chronic sinusitis and nasal concha hyperplasia. After the cells had been tested for vitality using the trypan blue exclusion test, the short-term culture method was used. The material was incubated with PCP (0.3, 0.75, and 1.2 mmol), lindane (0.5, 0.75, and 1.0 mmol), transfluthrin (0.05, 0.1, 0.5, 0.75, and 1.0 mmol), cyfluthrin (0.05, 0.1, 0.5, 0.75, and 1.0 mmol), natural pyrethrum (0.001, 0.005, 0.01, 0.05, and 0.1 mmol), and N-methyl-N'-nitro-N-nitrosoguanidine for 60 minutes. Substance-induced DNA damage (single-strand and double-strand breaks) were determined using single-cell microgel electrophoresis. A fluorescence microscope was used together with an image processing system to analyze the results obtained.


RESULTS
After exposure to all tested substances, a high percentage of the cells of the middle nasal concha in particular were found to have severely fragmented DNA as a result of strong genotoxic effects. Although the reaction of the cells of the inferior nasal concha was significantly less strong (p < 0.001), the tested substances were nevertheless found to have a notable genotoxic effect on these cells too.


CONCLUSIONS
Our study strongly suggests that exposure to PCP, lindane, transfluthrin, cyfluthrin, and natural pyrethrum has a genotoxic effect on the epithelial cells of human nasal mucosa. In addition, we have shown that nasal structures differ in susceptibility to the various pesticides used in the tests. Thus, the study provides new evidence supporting the biological plausibility of PCP- and lindane-induced effects, thereby helping evaluate potential PCP- and lindane-induced mucous membrane carcinomas of these parts of the nose. In addition, our study shows that other substances that today are widely used for controlling pests have a considerable genotoxic effect on human target cells. The results obtained indicate the need for additional studies on the genotoxicity of these substances and their adverse effects on human health.
Tisch
Matthias
M
Department of Otorhinolaryngology, Head and Neck Surgery, Bundeswehr Hospital, Ulm, Germany.
Faulde
Michael K
MK
Maier
Heinz
H
D000293:Adolescent; D000328:Adult; D011723:Chrysanthemum cinerariifolium / Q000633:toxicity*; D020552:Comet Assay; D004249:DNA Damage; D015180:Electrophoresis, Gel, Two-Dimensional; D004847:Epithelial Cells / Q000187:drug effects*; D005260:Female; D001556:Hexachlorocyclohexane / Q000633:toxicity*; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D008875:Middle Aged; D009153:Mutagens / Q000633:toxicity; D009297:Nasal Mucosa / Q000187:drug effects*; D009570:Nitriles / Q000633:toxicity*; D010416:Pentachlorophenol / Q000633:toxicity*; D011722:Pyrethrins / Q000633:toxicity*
D007306:Insecticides; D009153:Mutagens; D009570:Nitriles; D011722:Pyrethrins; D001556:Hexachlorocyclohexane; D010416:Pentachlorophenol; C052570:cyfluthrin