Assessment of Sister Chromatid Exchange in Spermatogonia and Intestinal Epithelium in Chinese Hamsters
The induction of sister chromatid exchange (SCE) has been proposed as a predictive test for the identification of mutagens/carci-nogens. The in vivo application of this test was investigated by examining the chemical induction of SCE in spermatogonia, intestinal epithelium and bone marrow cells from Chinese hamsters.
Sister chromatid differentiation (SCD) was achieved in differentiating spermatogonial cells of male Chinese hamsters by the abdominal subcutaneous (sc) implantation of an agar-coated bromode-oxyuridine (BrdUrd) tablet. A number of genotoxins were administered intraperitoneally (ip) and the induction of SCE in spermatogonia and bone marrow was compared. A significant increase in SCE frequency in spermatogonia occurred following treatment with mitomycin C (MMC), cyclophosphamide (CP), or N,N’,N"-triethylenethiophos-phoramide (ThioTEPA). Treatment with busulfan, hycanthone (HC), or triethylenemelamine (TEM) failed to induce SCE in vivo in spermatogonia, but these compounds did induce SCE in bone marrow. Differences in cell cycle kinetics were considered to be the major factor involved in the differential induction of SCE in spermatogonia and bone marrow.
The induction of SCE in intestinal epithelium was investigated as a system for the identification of genotoxins that may result from the metabolism of xenobiotics by the gastrointestinal flora. Nitro-aromatic compounds were administered orally to Chinese hamsters. Nitro-aromatic compounds were chosen for this study since the mutagenic activity of these compounds is thought to result from their metabolism by bacterial nitroreductase. Metronidazole (MN) and 2-nitro-p-phenylenediamine (2NPPD) induced a dose-related in crease in SCE formation in intestinal epithelium but not in bone marrow. Treatment with 3-nitro-o-phenylenediamine (3N0PD) or 4-nitro-£-phenylenediamine (4N0PD) did not induce the formation of SCE in either intestinal epithelium or bone marrow. These findings indicate that studies in axenic animals will be required to elucidate the contribution of the enteric flora to the metabolic activation of some genotoxins.
KeywordsBone Marrow Intestinal Epithelium Sister Chromatid Exchange Glacial Acetic Acid Spermatogonial Cell
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