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Type
HazMat fee for 500 gram (Estimated)
Excepted Quantity
USD 0.00
Limited Quantity
USD 15-60
Inaccessible (Haz class 6.1), Domestic
USD 80+
Inaccessible (Haz class 6.1), International
USD 150+
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Accessible (Haz class 3, 4, 5 or 8), International
Diethylnitrosamine (DEN) is a representative chemical carcinogen. DEN induces hepatocarcinogenesis, increasing mitotic hepatocytes and leading to chronic inflammation. Chronic DEN injections lead to liver damage, hepatocytes proliferation, liver fibrosis and cirrhosis, disorganized vasculature, and a modulated immune microenvironment that mimics the usual events observed during human HCC (Hepatocellular carcinoma) development. DEN-induced liver tumors in the rat model shared remarkable molecular characteristics with human HCC, especially with HCC associated with high proliferation[1]. All Cygb(+/-) and Cygb(-/-) mice treated with 25-ppm DEN exhibited liver tumors, compared with 44.4% of their wild-type counterparts. More than 40% of Cygb(-/-) mice developed liver and lung tumors at the nontoxic dose of DEN (0.05 ppm), which did not induce tumors in wild-type mice[2]. gp130 deletion in hepatocytes reduces progression, but not HCC initiation in the DEN model[3]. AR （androgen receptor） protein expression analyses show that DEN causes an initial upregulation of AR in portal fibroblasts and leukocytes, but not hepatocytes, suggesting that hepatocyte-autonomous AR signaling is not essential for DEN-induced carcinogenesis[4].
N-Nitrosodiethylamine 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Sprague-Dawley rats
DEN-induced liver cancer model
Gavage
0.002 g/rat
Four times a week for 14 weeks
Establish DEN-induced liver cancer model to study the hepatotoxicity mechanism of Rhubarb
Drug Des Devel Ther. 2024 Oct 9;18:4497-4510
Wistar rats
Liver cancer model
Oral administration via drinking water
0.1 mg/mL
Once daily for 20 weeks
To induce liver cancer and observe the effect of multi-stress conditions on cancer progression. Results showed that multi-stress significantly promoted the incidence of liver cancer and STAT3 expression.
Chin Med J (Engl). 2021 Jun 10;134(14):1762-1764
Mice
IPLA2β-null (KO) mice
Intraperitoneal injection
10 mg/kg
Single dose, duration 12 months
DEN-induced HCC protection by induction of cell-cycle arrest
Int J Mol Sci. 2022 Nov 9;23(22):13760
C57BL/6 mice
Zhx2wt and Zhx2KO mice
Intraperitoneal injection
10 mg/kg
Single injection, lasting 9 or 10 months
To investigate the role of Zhx2 in the DEN-induced HCC model, results showed that Zhx2KO mice had a complete absence of tumors after DEN treatment.
Short-term experiment: single injection followed by analysis at 24 and 48 hours; Long-term experiment: initial dose followed by weekly injections until 11 weeks of age, tumor evaluation at 30 weeks of age.
To investigate the role of HLJ1 in DEN-induced hepatocellular carcinoma. Results showed that HLJ1 deficiency enhances DEN-induced STAT3 and H2AX phosphorylation and increases tumor burden and progression.
Cell Biol Toxicol. 2024 Dec 30;41(1):20
BALB/c male mice
DEN-induced hepatocellular carcinoma
Intraperitoneal injection
120 mg/kg
Single dose, evaluated after 40 days
DEN was used to induce hepatocellular carcinoma model for evaluating the therapeutic effect of siRNA-bearing subtilosomes.
Molecules. 2023 Feb 27;28(5):2191
Mice
DEN-induced hepatocellular carcinoma model
Subcutaneous injection
15 μg/g
Single injection, continued until 8 months of age
To investigate the effect of HNF4α deletion on the progression of DEN-induced hepatocellular carcinoma. Results showed that HNF4α deletion significantly increased the number and size of tumors.
Hepatology. 2013 Jun;57(6):2480-90
Mice
DEN-induced HCC model
Intraperitoneal injection
15 μg/kg
Single injection, AAV8-TBG-Cre injection after 5 months, euthanized after 2 months
To investigate the effect of O-GlcNAcylation loss on DEN-induced HCC development. Results showed that OGT-KO mice exacerbated DEN-induced HCC development with increased inflammation, fibrosis, and YAP signaling, while OGA-KO mice inhibited DEN-induced HCC.
Hepatol Commun. 2023 Nov 6;7(11):e0283
New Zealand white rabbits
Pulmonary endocrine cell hyperplasia model
Subcutaneous injection
20 mg/kg
Twice per week, lasting 6 to 8.5 months
To determine whether DEN can induce pulmonary endocrine cell hyperplasia and its association with adenomatosis and adenocarcinoma in rabbits. Results showed that DEN induced not only endocrine cell hyperplasia but also adenomatosis and adenocarcinomas.
Am J Pathol. 1989 Dec;135(6):1119-28
Mice
Humanized transgenic mouse model
Intraperitoneal injection
20 mg/kg
Single injection, followed by 39 weeks
To investigate the effect of UGT1A polymorphisms on DEN-induced hepatocellular carcinoma development. Results showed that mice carrying UGT1A SNPs had significantly increased tumor number and cumulative diameter, while coffee cotreatment reduced tumor incidence.
Cancer Sci. 2020 Nov;111(11):4266-4275
C57/BL6 mice
DEN/CCl4-induced hepatic fibrosis model
Intraperitoneal injection
20 mg/kg DEN and 5 mL/kg CCl4
DEN once a week for 2 weeks; CCl4 three times a week for 6 weeks
Establish hepatic fibrosis model and evaluate the therapeutic effect of ADSC-EXO
Stem Cell Res Ther. 2022 Oct 4;13(1):494
Wistar rats
Adult male Wistar rats
Intraperitoneal injection
200 mg/kg
Single dose, sacrificed at 1, 3, 7, and 35 days after injection
To investigate the effects of DEN on pituitary ultrastructure, serum levels of several hormones, as well as expression and activities of several sex-differentiated liver enzymes. The results showed that DEN can cause pituitary damage, disturb serum hormone levels, and reduce the sexual dimorphism of certain liver functions.
Environ Health Perspect. 2001 Sep;109(9):943-7
Wistar albino rats
Hepatic carcinogenesis model
Intraperitoneal injection
200 mg/kg
Single injection
To investigate whether carnitine deficiency is a risk factor during the development of DENA-induced hepatic carcinogenesis. Results showed that DENA significantly increased serum ALT, G-GT, ALP, and total bilirubin, and significantly decreased total carnitine content in liver tissues. Carnitine depletion aggravated DENA-induced liver damage, while L-carnitine supplementation completely reversed these changes induced by DENA.
World J Gastroenterol. 2009 Mar 21;15(11):1373-80
C57BL/6N mice
Hepatocellular carcinoma model
Intraperitoneal injection
25 mg/kg
Single injection, observed until 32 weeks of age
To investigate the effects of dietary fats and sugars on DEN-induced hepatocellular carcinoma tumor burden. Results showed that high-sugar diets significantly increased tumor burden, while high-fat low-sugar diets had the least tumor burden.
J Hepatol. 2015 Mar;62(3):599-606
Mice
Hepatocyte-specific KCTD17 deficient mice
Intraperitoneal injection
25 mg/kg
Single injection
Assess the effect of DEN on HCC progression
Clin Mol Hepatol. 2024 Oct;30(4):895-913
Mice
DEN-induced primary liver cancer model
Intraperitoneal injection
25 mg/kg
Single injection
To induce primary liver cancer model for studying the effect of CD5-2 and anti-PD1 antibody on liver tumor growth, vasculature and immune infiltrate.
Front Immunol. 2023 Sep 18;14:1245708
Male albino rats (Wistar strain)
DEN-induced hepatocellular carcinoma model
Intraperitoneal injection
25 mg/kg
Single dose, analyzed after 4 months
DEN was used to induce hepatocellular carcinoma in rats, leading to DNA damage through DNA alkylation and oxidative stress.
Front Immunol. 2024 Jan 15;14:1206990
Male C57BL/6 mice
DEN-induced murine hepatocarcinogenesis model
Intraperitoneal injection
25 mg/kg
Single administration
After a single intraperitoneal administration of DEN (25 mg/kg), liver tumor formation was observed in 100% of male mice after 8–10 months.
Int J Mol Sci. 2022 May 12;23(10):5397
Wistar rats
Hepatocellular carcinoma model
DEN intraperitoneal injection, 2-AAF intragastric administration
DEN 50 mg/kg/week, 2-AAF 25 mg/kg/week
Weekly for 18 weeks
To induce hepatocellular carcinoma and observe biochemical, histological, and gene expression changes. Results showed significant increases in total cholesterol, HDL-C, AST, ALT, ALKP, and GGT levels in the treated group, loss of normal liver architecture, increased fibrosis, and significant gene expression changes.
DENA: once per week for 2 weeks; AAF: four times per week for 3 weeks
To evaluate the DENA/AAF-induced lung cancer model, results showed DENA/AAF caused lung histological lesions including sheets of tumor cells, micropapillary adenocarcinoma, and apoptotic cells
Apoptosis. 2023 Aug;28(7-8):1184-1197
C57BL/6 mice
Hepatocellular carcinoma model
Intraperitoneal injection
Initial dose 20 mg/kg, 30 mg/kg in the third week, followed by 50 mg/kg for the last six weeks
Eight doses in total, lasting 24 weeks
Establish an animal model of hepatocellular carcinoma, results showed high tumor incidence and low mortality rate.
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