DETECTION OF GENOTOXIC EFFECTS IN HUMAN GASTRIC AND NASAL-MUCOSA CELLS ISOLATED FROM BIOPSY SAMPLES

To assess genotoxic burdens from chemicals, it is necessary to relate observations in experimental animals to humans. The success of this ex trapolation would be increased by including data on chemical activitie s in human tissues. Therefore, we have developed techniques to assess DNA damage in human gastric and nasal mucosa (GM, NM) cells. Biopsy sa mples were obtained during gastroscopy from macroscopically healthy ti ssue of the stomach or from healthy nasal epithelia during surgery. Th e specimens were incubated for 30-45 min at 37 degrees C with a digest ive solution. We obtained 1.5-8 x 10(6) GM cells and 5-10 x 10(5) NM c ells per donor, both with viabilities of 80-95%. The cells were incuba ted 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 sulph ate (NiSO4), cadmium sulphate (CdSO4), and lindane. In NM cells, linda ne was investigated. Each compound was assessed for DNA damaging activ ity in cells of at least three different human donor samples using the microgel single cell assay. Similar studies were performed with GM an d NM cells obtained from Sprague-Dawley rats. We have found human GM c ells to be more sensitive to the genotoxic activity of MNNG than rat G M cells (low effective concentration [LEC] = 0.16 and 0.625 mu g/ml fo r human and rat, respectively). Human cells were also more sensitive t o the cytotoxic/genotoxic activity of NiSO4 (LEC = and 19 mu moles/ml for human and rat, respectively). CdSO4 was genotoxic in human GM cell s (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 co ntrast, approximately equal responses regarding genotoxicity and cytot oxicity were observed in rat and human GM for Na2Cr2O7 (0.25-1 mu mole s/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 b oth rat and human NM cells. Together with other recently published in vivo findings, our results with lindane can be interpreted according t o a parallelogram approach. In view of possible human exposure situati ons and the sensitivities of the two target tissues from both species, the data imply that [indane will pose a health risk to humans by inha lation but not by ingestion. (C) 1994 Wiley-Liss, Inc.