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Titolo:
DETECTION OF GENOTOXIC EFFECTS IN HUMAN GASTRIC AND NASAL-MUCOSA CELLS ISOLATED FROM BIOPSY SAMPLES
Autore:
POOLZOBEL BL; LOTZMANN N; KNOLL M; KUCHENMEISTER F; LAMBERTZ R; LEUCHT U; SCHRODER HG; SCHMEZER P;
Indirizzi:
BUNDESFORSCH ANSTALT ERNAHRUNG,INST HYG & TOXIKOL,ENGESSERSTR 20 D-76131 KARLSRUHE GERMANY DEUTSCH KREBSFORSCHUNGSZENTRUM,TOXIKOL & KREBSRISIKOFAKTOREN ABT W-6900 HEIDELBERG GERMANY UNIV MARBURG,HALS NASEN OHREN KLIN W-3550 MARBURG GERMANY KREISKRANKENHAUS,GASTROENTEROL ABT SCHWETZINGEN GERMANY
Titolo Testata:
Environmental and molecular mutagenesis
fascicolo: 1, volume: 24, anno: 1994,
pagine: 23 - 45
SICI:
0893-6692(1994)24:1<23:DOGEIH>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
UNSCHEDULED DNA-SYNTHESIS; HEPATOCYTE PRIMARY CULTURES; SPRAGUE-DAWLEY RATS; UNITED-STATES; UDS ASSAY; INVIVO; REPAIR; CARCINOGENESIS; CANCER; INDUCTION;
Keywords:
IN VITRO GENOTOXICITY; DNA DAMAGE; METAL SALTS; CADMIUM; NICKEL; CHROMIUM; N-METHYL-N'-NITRO-N-NITROSOGUANIDINE (MNNG); LINDANE; HUMAN BIOPSY SAMPLES; MICROGEL SINGLE CELL ASSAY; COMET ASSAY; PARALLELOGRAM APPROACH; GASTRIC MUCOSA CELLS; NASAL MUCOSA CELLS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
65
Recensione:
Indirizzi per estratti:
Citazione:
B.L. Poolzobel et al., "DETECTION OF GENOTOXIC EFFECTS IN HUMAN GASTRIC AND NASAL-MUCOSA CELLS ISOLATED FROM BIOPSY SAMPLES", Environmental and molecular mutagenesis, 24(1), 1994, pp. 23-45

Abstract

To assess genotoxic burdens from chemicals, it is necessary to relateobservations in experimental animals to humans. The success of this extrapolation would be increased by including data on chemical activities in human tissues. Therefore, we have developed techniques to assessDNA damage in human gastric and nasal mucosa (GM, NM) cells. Biopsy samples were obtained during gastroscopy from macroscopically healthy tissue of the stomach or from healthy nasal epithelia during surgery. The specimens were incubated for 30-45 min at 37 degrees C with a digestive solution. We obtained 1.5-8 x 10(6) GM cells and 5-10 x 10(5) NM cells per donor, both with viabilities of 80-95%. The cells were incubated in vitro for 1 hr at 37 degrees C with the test compounds added in their appropriate solvents. In GM cells, we studied N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), sodium dichromate (Na2Cr2O7), nickel sulphate (NiSO4), cadmium sulphate (CdSO4), and lindane. In NM cells, lindane was investigated. Each compound was assessed for DNA damaging activity in cells of at least three different human donor samples using the microgel single cell assay. Similar studies were performed with GM and NM cells obtained from Sprague-Dawley rats. We have found human GM cells to be more sensitive to the genotoxic activity of MNNG than rat GM cells (low effective concentration [LEC] = 0.16 and 0.625 mu g/ml for human and rat, respectively). Human cells were also more sensitive to the cytotoxic/genotoxic activity of NiSO4 (LEC = and 19 mu moles/mlfor human and rat, respectively). CdSO4 was genotoxic in human GM cells (LEC = 0.03-0.125 mu moles/ml), whereas no dose-related genotoxicity was observed in rat GM at concentrations vp to 0.5 mu moles/ml. In contrast, approximately equal responses regarding genotoxicity and cytotoxicity were observed in rat and human GM for Na2Cr2O7 (0.25-1 mu moles/ml). Lindane, however, was genotoxic in three out of four rat GM but not in human GM cells (0.5-1 mu moles/ml), whereas it was active in both rat and human NM cells. Together with other recently published invivo findings, our results with lindane can be interpreted according to a parallelogram approach. In view of possible human exposure situations and the sensitivities of the two target tissues from both species, the data imply that [indane will pose a health risk to humans by inhalation but not by ingestion. (C) 1994 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 22:46:39