使用亚硝基二乙胺可以在动物中建立肝纤维化模型。

Absorption, Distribution and Excretion
/MILK/ In goats, 1 hr after oral administration of 30 mg/kg bw nitrosodiethylamine, there were 11.4 mg/kg nitrosodiethylamine in milk and 11.9 mg/kg in blood. Only traces were found in milk and none in blood after 24 hr.
Autoradiographic studies indicated that non-metabolized N-nitrosodiethylamine passed to fetuses with even distribution in most fetal tissues on all studied days of gestation (day 12, 14, 16, 16 and 18) in mice. Results also indicated metabolism of the substance in mucosa of fetal bronchial tree and liver on day 18 of gestation.

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Metabolism / Metabolites
Inhibition of sulfotransferase by 2,6-dichloro-4-nitrophenol completely abolished the genotoxic potential of N-nitrosodiethanolamine in rat liver as indicated by the induction of DNA single-strand breaks. The DNA strand-breaking potential of N-nitroso-2-hydroxymorpholine, a metabolite of N-nitrosodiethanolamine formed by alcohol dehydrogenase -mediated oxidation, was also almost quantitatively abolished. In contrast to these beta-hydroxylated nitrosamines, the effectiveness of N-nitrosodiethylamine remained unaffected by 2,6-dichloro-4-nitrophenol with respect to its DNA damaging potential. ... A new activation mechanism for N-nitrosodiethanolamine is proposed: N-nitrosodiethanolamine is transformed at first by alcohol dehydrogenase into the cyclic hemiacetal N-nitroso-2-hydroxymorpholine. This cyclic beta-hydroxynitrosamine appears to be a substrate for sulfotransferase. The resulting sulfate conjugate is suggested to be ultimate genotoxic electrophile. However, the results do not exclude the possibility that N-nitrosodiethanolamine itself undergoes sulfate conjugation.
Oxidative N-deethylation of NDEA accounts for the production of CO2 and alkylating species in vivo. The rate of metabolism of NDEA by slices of organs from rats and hamsters in vitro has been measured, and a correlation made between the degree of metabolism and the distribution of induced tumors. After administration of NDEA to rats or hamsters, several ethylated derivatives were produced in liver and kidney nucleic acids. These included 7-ethylguanine, O6-ethylguanine and 3-ethyladenine.
... Evidence suggests that nitrosodiethylamine requires metabolic activation in order to exert its carcinogenic and toxic effects. ... N-nitrosoethyl-N-(2-hydroxyethyl)amine and N-nitrosoethyl-N-(carboxymethyl)amine have been detected in urine of rats. ...
Possible relationships between structure and metabolism of nitrosamines have been investigated in the rat small intestine. Isolated segments of jejunum and ileum were perfused from the luminal side for 2 hr with a Tyrode solution containing one of four symmetrical dialkylnitrosamines with 2-5 carbon atoms per side chain, all (14)C-labeled at the alpha position, or one of two unsymmetrical nitrosamines, N-nitroso-tert-butylmethylamine and N-nitrosomethylbenzylamine, (14)C-labeled in the methyl group. Besides measurement of (14)C to intestinal tissue, the absorbed fluid (absorbate) as well as the perfusion medium and tissue homogenates were analyzed by for the presence of polar metabolites to assess the intestinal metabolism of nitrosamines. Neither N-nitrosodiethylamine nor the two unsymmetrical nitrosamines were metabolized to any significant extent.
Nitrosodiethylamine has known human metabolites that include N-Nitrosoethanamine.

[1]. Suppression of N-nitrosodiethylamine induced hepatocarcinogenesis by silymarin in rats. Chem Biol Interact. 2006 Jun 10;161(2):104-14.

[2]. Protective role of Vitamin E pre-treatment on N-nitrosodiethylamine induced oxidative stress in rat liver. Chem Biol Interact. 2005 Oct 20;156(2-3):101-11.

[3]. Pharmacokinetics of N-nitrosodimethylamine in beagles. Cancer Res. 1987 Jan 15;47(2):343-7.

[4]. N-nitrosodiethylamine mechanistic data and risk assessment: bioactivation, DNA-adduct formation, mutagenicity, and tumor initiation. Pharmacol Ther. 1996;71(1-2):57-81.

n-Nitrosodiethylamine can cause cancer according to an independent committee of scientific and health experts.
N-nitrosodiethylamine is a clear slightly yellow liquid. Boiling point 175-177 °C. Can reasonably be anticipated to be a carcinogen. Used as a gasoline and lubricant additive and as an antioxidant and stabilizer in plastics.
N-nitrosodiethylamine is a nitrosamine that is N-ethylethanamine substituted by a nitroso group at the N-atom. It has a role as a mutagen, a hepatotoxic agent and a carcinogenic agent.
N-Nitrosodiethylamine is a synthetic light-sensitive, volatile, clear yellow oil that is soluble in water, lipids, and other organic solvents. It is used as gasoline and lubricant additive, antioxidant, and stabilizer for industry materials. When heated to decomposition, N-nitrosodiethylamine emits toxic fumes of nitrogen oxides. N-Nitrosodiethylamine affects DNA integrity, probably by alkylation, and is used in experimental research to induce liver tumorigenesis. It is considered to be reasonably anticipated to be a human carcinogen. (NCI05)
A nitrosamine derivative with alkylating, carcinogenic, and mutagenic properties.

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Mechanism of Action
... It is shown that the two nitrosamines N-nitrosodiethylamine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone bind to nicotinic cholinergic receptors in hamster lung. Binding of the nitrosamines as well as nicotine to this receptor stimulates proliferation of human lung carcinoid cells in vitro. These data suggest chronic stimulation of nicotinic receptors by nicotine and nitrosamines in smokers as one of the molecular events responsible for stimulation of neuroendocrine cell proliferation and ultimately the development of lung tumors with neuroendocrine differentiation. ...

C4H10N2O

102.14

102.079

55-18-5

N-Nitrosodiethylamine-d4;1346603-41-5;N-Nitrosodiethylamine-d10;1219794-54-3

5921

Colorless to light yellow liquid

0.9±0.1 g/cm3

173.9±9.0 °C at 760 mmHg

<25℃

59.0±18.7 °C

1.7±0.3 mmHg at 25°C

1.442

0.42

32.67

0

3

2

7

51.7

0

CCN(CC)N=O

WBNQDOYYEUMPFS-UHFFFAOYSA-N

InChI=1S/C4H10N2O/c1-3-6(4-2)5-7/h3-4H2,1-2H3

N,N-diethylnitrous amide

DEN; Diethylnitrosamine; N-Nitrosodiethylamine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~100 mg/mL (~979.1 mM)
DMSO : ~100 mg/mL (~979.1 mM)

配方 1 中的溶解度: ≥ 2.5 mg/mL (24.48 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (24.48 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.5 mg/mL (24.48 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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配方 4 中的溶解度: 100 mg/mL (979.05 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶 (<60°C).

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。