DEN shows liver-specific toxicity, as a result it is mostly used to induce various kinds of liver cancer. But there seem to be a lot of heterogeneity in the method of administration of DEN.
Hi Alex,
In our lab for rats we give 0.01% DEN in drinking water for 15 weeks. This model works very good in rats with a liver tumor incidence of 100%. Please see the attached papers for more details.
Good luck with your research.
Ram
I inject i.p. once only into 14 day old pups, dose of 5 mg/kg. Tumours appear at 8-9 months depending on diet. Published dose varies between 5 and 25 mg/kg, others I have worked with found that 25 mg/kg caused a significant number of pups to die immediately after injection.
I.p. works for the resistant hepatocyte model in dose of 20 mg/ kg, single dose combined with 2AAF and partial hepatectomy, and there is another model with one dose per week of 50 mg/kg and at week 16-18 you can se tummors
I.p. works for the resistant hepatocyte model in dose of 20 mg/ kg, single dose combined with 2AAF and partial hepatectomy, and there is another model with one dose per week of 50 mg/kg and at week 16-18 you can se tummors
Hi Alex,
We used the protocol #1 in this publication (Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression. Park EJ, Lee JH, Yu GY, He G, Ali SR, Holzer RG, Osterreicher CH, Takahashi H, Karin M.
Cell. 2010 Jan 22;140(2):197-208.) What we did is: 3 weeks mice, DEN 25 mg/kg IP, switch to HFD, we are waiting for the 18 weeks to deliver our gene therapy, then collect tissue on weeks 36. We don't know the result yet. But it seems a very good paper, you may take a look.
Diethylnitrosamine or DEN-induced mouse model of HCC was described way back in 1966 by Rajewsky et al (Science 152:83,85). Now DEN is routinely used in combination with Phenobarbital to get best results. The protocol is as follows:
Take 6 weeks old male mice (usually C3H/He strain) and give a single intra-peritoneal injection of DEN (90 microgram/kg body weight). Feed these mice with phobarbital (0.07% w/w) in standard diet, starting 2 weeks after DEN injection. Observe the animals beyond 32 weeks post DEN injection for tumor formation.
Further Reading:
Bakiri and Wagner, Molecular Oncology 7: 206-223, 2013
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