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分析N-亚硝胺在源自不同物种的原代肝细胞中的遗传毒性。

Analysis of N-nitrosamines for genotoxicity in primary hepatocytes derived from various species.

作者信息

Schmezer P, Pool B L, Preussmann R, Schmähl D

机构信息

Institute for Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg.

出版信息

IARC Sci Publ. 1987(84):270-3.

PMID:3679384
Abstract

DNA single-strand breaks (SSB) were induced in metabolically competent primary hepatocytes from rats, hamsters and pigs by a series of N-nitrosamines with organ-specific activities. Both hepatotrophic and nonhepatotropic carcinogens were genotoxic in the liver cells of all three species. Nonhepatotropic compounds were active at relatively lower doses than liver carcinogens in all species tested, substantiating many previous findings that organ-specific activation is not the primary determining factor of organ susceptibility to cancer. In 11 experiments of almost identical quality, the degree of SSB induced by 6.25 mumol N-nitrosodimethylamine varied by 75%. This high interindividual variability, even among hepatocytes derived from a single rat strain, indicates that the slight differences seen between rat, hamster and pig hepatocytes are not necessarily due to differences in species susceptibility.

摘要

一系列具有器官特异性活性的N-亚硝胺在大鼠、仓鼠和猪的代谢活性原代肝细胞中诱导产生DNA单链断裂(SSB)。肝营养性致癌物和非肝营养性致癌物在所有这三个物种的肝细胞中均具有基因毒性。在所有测试物种中,非肝营养性化合物在相对较低剂量时就具有活性,这比肝脏致癌物的活性剂量低,证实了许多先前的研究结果,即器官特异性活化不是器官对癌症易感性的主要决定因素。在11个质量几乎相同的实验中,6.25μmol N-亚硝基二甲胺诱导的SSB程度相差75%。这种高度的个体间变异性,即使在来自单一大鼠品系的肝细胞之间也是如此,表明在大鼠、仓鼠和猪肝细胞之间观察到的细微差异不一定是由于物种易感性的差异。

相似文献

1
Analysis of N-nitrosamines for genotoxicity in primary hepatocytes derived from various species.分析N-亚硝胺在源自不同物种的原代肝细胞中的遗传毒性。
IARC Sci Publ. 1987(84):270-3.
2
Measurements by filter elution of DNA single- and double-strand breaks in rat hepatocytes: effects of nitrosamines and gamma-irradiation.大鼠肝细胞中DNA单链和双链断裂的滤膜洗脱法测量:亚硝胺和γ射线辐射的影响
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Organ specific genotoxicity and carcinogenicity.器官特异性遗传毒性和致癌性。
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Comparative study of DNA damage and repair induced by ten N-nitroso compounds in primary cultures of human and rat hepatocytes.十种N-亚硝基化合物对原代人肝细胞和大鼠肝细胞DNA损伤及修复的比较研究
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Comparison of induction of DNA single-strand breaks and initiation of rat hepatocarcinogenesis by different nitrosamines.不同亚硝胺诱导大鼠DNA单链断裂及引发肝癌发生的比较。
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Formation of the N-nitroso derivatives of six beta-adrenergic-blocking agents and their genotoxic effects in rat and human hepatocytes.六种β-肾上腺素能阻滞剂的N-亚硝基衍生物的形成及其对大鼠和人肝细胞的遗传毒性作用。
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