Cytochemical and biochemical studies on adenylate cyclase activity in preneoplastic and neoplastic liver tissue and cultured liver cells

Mayer, Doris; Klimek, Fritz; Bannasch, Peter

doi:10.1002/(sici)1097-0029(19980301)40:6<463::aid-jemt6>3.0.co;2-q

Cited by 5 publications

(1 citation statement)

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“…Administration of the N-nitrosamine N-nitrosomorpholine (NNM) in rats is a well-examined model of chemically induced hepatocarcinogenesis (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). Weber and Bannasch have used several dosage protocols of NNM administration (4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Cocarcinogenic Effects of Islet Hormones and N-Nitrosomorpholine in Hepatocarcinogenesis after Intrahepatic Transplantation of Pancreatic Islets in Streptozotocin-Diabetic Rats

et al. 2005

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In contrast to high local insulin levels obtained after lownumber transplantation (n = 350) of islets of Langerhans into the livers of diabetic rats, low insulin levels after high-number transplantation (n = 1,000) do not suffice to induce hepatocarcinogenesis. Herein, we investigated the possible cocarcinogenic potential of high and, in particular, low insulin levels, combining this in vivo model with a chemical model of hepatocarcinogenesis after administration of Nnitrosomorpholine (NNM). In three main experiments, different schemes of single or continuous NNM administration were combined with different transplantation procedures in diabetic or nondiabetic animals, i.e., low-number and highnumber islet transplantation, transplantation of polystyrene particles, and sham transplantation. Animals were sacrificed between 3 and 53 weeks after transplantation procedures. Evidence for the cocarcinogenic effects of NNM and insulin was provided in each main experiment. NNM treatment after low-number islet transplantation resulted in an increase in the number of preneoplastic hepatocellular foci, and a significant increase in the number and an earlier appearance of hepatocellular adenomas and carcinomas compared with controls. Most intriguing was the increase in preneoplastic foci after combined NNM treatment and high-number islet transplantation, proving that insulin, even in lower doses, has at least cocarcinogenic effects on the downstream hepatocytes and thus promotes an otherwise initiated hepatocarcinogenic process. Conclusively, intrahepatic transplantation of pancreatic islets acts as a strong cocarcinogenic factor together with NNM in streptozotocin-diabetic rats. (Cancer Res 2005; 65(15): 7013-22)

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