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用N-亚硝基化合物处理的小鼠肝脏中致癌物代谢能力的改变。

Modifications in the carcinogen-metabolizing capacity of mouse liver treated with N-nitroso compounds.

作者信息

Habib S L, Badawi A F, Aweny H A, Mostafa M H

机构信息

Department of Environmental Studies, Institute of Graduate Studies and Research, Alexandria University, Alexandria, Egypt.

出版信息

Oncol Rep. 1998 Jul-Aug;5(4):965-9. doi: 10.3892/or.5.4.965.

DOI:10.3892/or.5.4.965
PMID:9625856
Abstract

One tenth of the LD50 as a single dose of various N-nitroso compounds (N-nitrosodimethylamine; NDMA, N-nitrosodiethylamine; NDEA, N-nitrosoethylpropylamine; NEPA, N-nitrosodipropylamine; NDPA, N-nitrosomethylethylamine; NMEA, N-nitroso-methylbutylamine; NMBA and N-nitrosoethylbutylamine; NEBA) was administrated into male mice. This dose markedly increased the hepatic contents of cytochrome P450 and cytochrome b5 and activities of NADPH-cytochrome c reductase and aryl hydrocarbon hydroxylase (AHH). The highest increase in the activity of cytochrome P450 (+142% relative to the control value) was shown in animals treated with either N-nitrosoethylpropylamine or N-nitrosodiethylamine. On the other hand, the lowest increase in the activity (+16%) was revealed in animals treated with N-nitrosodimethylamine (not significant compared to the control value). Cytochrome b5 content was increased by 190% of the control value in mice treated with N-nitrosomethylbutylamine, while N-nitrosodibutylamine induced the lowest increase (+20%). The maximum increase (+182%) in the activity of aryl hydrocarbon hydroxylase was shown in animals which received N-nitrosomethylbutylamine, while the lowest increase (+23%) in animals which received N-nitrosodiethylamine. The activity of hepatic AHH was also increased above the control value in animals treated with NDMA, NEBA NDPA, NMEA and NDBA by 138, 98, 90, 89 and 69%, respectively. Identically, NADPH-cytochrome c reductase activity was increased in animals which received NEPA, NMBA, NDMA, NMEA, NDPA, NEBA and NDEA by 202, 150, 110, 95, 94, 77 and 37%, respectively.

摘要

将各种N-亚硝基化合物(N-亚硝基二甲胺;NDMA、N-亚硝基二乙胺;NDEA、N-亚硝基乙丙胺;NEPA、N-亚硝基二丙胺;NDPA、N-亚硝基甲乙胺;NMEA、N-亚硝基甲基丁胺;NMBA和N-亚硝基乙丁胺;NEBA)单剂量的十分之一LD50给予雄性小鼠。该剂量显著增加了细胞色素P450和细胞色素b5的肝脏含量以及NADPH-细胞色素c还原酶和芳烃羟化酶(AHH)的活性。用N-亚硝基乙丙胺或N-亚硝基二乙胺处理的动物中,细胞色素P450活性增加最高(相对于对照值增加142%)。另一方面,用N-亚硝基二甲胺处理的动物中活性增加最低(16%)(与对照值相比无显著差异)。用N-亚硝基甲基丁胺处理的小鼠中,细胞色素b5含量增加到对照值的190%,而N-亚硝基二丁胺诱导的增加最低(20%)。接受N-亚硝基甲基丁胺的动物中芳烃羟化酶活性增加最大(182%),而接受N-亚硝基二乙胺的动物中增加最低(23%)。用NDMA、NEBA、NDPA、NMEA和NDBA处理的动物中,肝脏AHH活性也分别比对照值增加了138%、98%、90%、89%和69%。同样,接受NEPA、NMBA、NDMA、NMEA、NDPA、NEBA和NDEA的动物中,NADPH-细胞色素c还原酶活性分别增加了202%、150%、110%、95%、94%、77%和37%。

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