Glatt H, Gemperlein I, Setiabudi F, Platt K L, Oesch F
Department of Toxicology, University of Mainz, FRG.
Mutagenesis. 1990 May;5(3):241-9. doi: 10.1093/mutage/5.3.241.
Activities of various xenobiotic-metabolizing enzymes were determined in 18 cell lines. Activities of cytochrome P450 reductase, microsomal epoxide hydrolase and glutathione transferase were detectable in all lines. The highest values were similar to the activities found in freshly isolated rat hepatocytes. Catalase activity was also present in all 12 investigated cell lines. Activity of UDP-glucuronosyl transferase was high in some lines, but low or undetectable in others. Activity of cytosolic epoxide hydrolase was not measurable in most lines, and was low in the others. Metabolism of benzo[a]pyrene was observed in eight out of nine examined lines, no activity being found in V79 cells. V79 and three epithelial cell lines were then used as target cells in a genotoxicity assay in which the frequency of micronucleated cells was determined. In V79 cells, 7,12-dimethyl- benz[a]anthracene, benzo[a]pyrene, benzo[a]pyrene-trans-7,8-dihydrodiol, aflatoxin B1, N-nitrosomorpholine and 2-acetylaminofluorene showed negative responses, whereas N-methyl-N'-nitro-N-nitrosoguanidine, 9-hydroxybenzo[a]pyrene, 2-nitrofluorene, dibenz[a,h]anthracene 1,2-catechol, dibenz[a,h]anthracene, 1,2-quinone hydroquinone and p-benzoquinone proved positive in the test. All 13 compounds, however, induced micronuclei in rat intestinal cells (IEC-17 and IEC-18) and in embryonal human liver cells (HuFoe-15). Thus, these epithelial cell lines are capable of activating and detecting a broad spectrum of chemically diverse genotoxic compounds. They may also be useful for the detection of hazardous compounds whose active metabolites are not able to penetrate from the extracellular space into the indicator cell.
在18种细胞系中测定了各种外源性物质代谢酶的活性。在所有细胞系中均检测到细胞色素P450还原酶、微粒体环氧化物水解酶和谷胱甘肽转移酶的活性。最高值与新鲜分离的大鼠肝细胞中的活性相似。在所有12种被研究的细胞系中也存在过氧化氢酶活性。尿苷二磷酸葡萄糖醛酸基转移酶的活性在某些细胞系中较高，但在其他细胞系中较低或无法检测到。在大多数细胞系中无法测量胞质环氧化物水解酶的活性，在其他细胞系中活性较低。在9种检测的细胞系中有8种观察到苯并[a]芘的代谢，在V79细胞中未发现活性。然后，将V79和三种上皮细胞系用作遗传毒性试验的靶细胞，在该试验中测定微核细胞的频率。在V79细胞中，7,12-二甲基苯并[a]蒽、苯并[a]芘、苯并[a]芘反式-7,8-二氢二醇、黄曲霉毒素B1、N-亚硝基吗啉和2-乙酰氨基芴呈阴性反应，而N-甲基-N'-硝基-N-亚硝基胍、9-羟基苯并[a]芘、2-硝基芴、二苯并[a,h]蒽1,2-儿茶酚、二苯并[a,h]蒽、1,2-醌氢醌和对苯醌在试验中呈阳性。然而，所有13种化合物均在大鼠肠细胞（IEC-17和IEC-18）和人胚胎肝细胞（HuFoe-15）中诱导微核。因此，这些上皮细胞系能够激活和检测广泛的化学性质不同的遗传毒性化合物。它们也可能有助于检测其活性代谢产物无法从细胞外空间穿透到指示细胞中的有害化合物。
