Production of DNA strand breaks by N-nitrosodimethylamine and 2-amino-3-methylimidazo[4,5-f]quinoline in THLE cells expressing human CYP isoenzymes and inhibition by sulforaphane
Production of DNA strand breaks by N-nitrosodimethylamine and 2-amino-3-methylimidazo[4,5-f]quinoline in THLE cells expressing human CYP isoenzymes and inhibition by sulforaphane
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DOI：
10.1016/s0027-5107(97)00288-1
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发表时间：
1998-06-18
影响因子：
2.3
通讯作者：
Chipman, JK
中科院分区：
文献类型：
--
作者：
Barceló, S;Macé, K;Chipman, JK
使用彗星测定法，分别在 T5-2E1（表达人 CYP2E1）和 T5-1A2（表达人 CYP1A2）人肝细胞中观察到 N-亚硝基二甲胺 (NDMA) 和 2-氨基-3-甲基咪唑[4,5-f]喹啉 (IQ) 产生 DNA 链断裂。反应具有统计学显着性（P < 0.05）且具有浓度依赖性（0.01-1 μg ml(-1) NDMA 和 0.1-10 μg ml(-1) IQ），并且在缺乏细胞色素 P450 活性的 TS-neo 细胞中未观察到。萝卜硫素（1-异硫氰酸酯-4-甲基亚磺酰丁烷）（0.1-10 μM）对这些致癌物造成的 DNA 链断裂具有显着抑制作用（P < 0.05 线性回归）。这是在不存在细胞毒性且不抑制 H2O2 诱导的 DNA 链断裂的情况下观察到的。因此，萝卜硫素抑制 CYP2E1 和 CYP1A2 介导的基因毒性的能力与这些酶的人类亚型相关，并且可能有助于化学预防活性。 (C) 1998 Elsevier Science B.V. 保留所有权利。
The production of DNA strand breaks by N-nitrosodimethylamine (NDMA) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) has been observed in T5-2E1 (expressing human CYP2E1) and T5-1A2 (expressing human CYP1A2) human liver cells respectively, using the Comet assay. Responses were statistically significant (P < 0.05) and concentration dependent (0.01-1 mu g ml(-1) NDMA and 0.1-10 mu g ml(-1) IQ) and were not observed in TS-neo cells devoid of cytochrome P450 activity. Sulforaphane (1-isothiocyanate-4-methylsulfinylbutane) (0.1-10 mu M) gave a marked inhibition of DNA strand breakage by these carcinogens (P < 0.05 linear regression). This was seen in the absence of cytotoxicity and in the absence of an inhibition of H2O2-induced DNA strand breakage. The ability of sulforaphane to inhibit both CYP2E1 and CYP1A2-mediated genotoxicity therefore is relevant to human isoforms of these enzymes and may contribute to a chemopreventative activity. (C) 1998 Elsevier Science B.V. All rights reserved.