Anin vitro model of human pancreas carcinogenesis: Effects of nitroso compounds

Abstract

It has been possible to maintain adult human pancreas in organ culture in a chemically defined medium. Under these conditions, all cell types demonstrated at least a limited ability to proliferate. This in vitro model was employed to study the effects of three nitroso compounds, DMNA, MNU, and BHP, on adult human pancreas. The major effects of three nitroso compounds, DMNA, MNU, and BHP, on adult human pancreas. The major effects of these compounds in cytotoxicity, proliferation, and oncogenicity was evaluated morphologically. DMNA and MNU were both carcinogenic but with varying rapidity of induction. MNU produced greater necrosis but gave more rapid induction. BHP produced cytotoxicity sufficient to prevent any rating of its oncogenic potential. Morphologically malignant tissue were tested for growth potential in nude mice. All nude mice developed multiple subcutaneous tumor nodules within eight weeks after inoculation. The tumor nodules ranged morphologically from undifferentiated scirrhous carcinoma to well-differentiated papillary adenocarcinoma.

Does the Use of Proton Pump Inhibitors Increase the Risk of Pancreatic Cancer? A Systematic Review and Meta-Analysis of Epidemiologic Studies

“…Faster nitrosation of luminal amines triggers the production of potentially carcinogenic N-nitrosamines in the lumen [ 66 ]. Pancreatic ductal adenocarcinomas have been found in nitrosamine-exposed mice and human pancreatic cells (in vitro) [ 67 ]. N-nitrosamine carcinogens attribute DNA damage by forming methyl and 2-hydroxypropyl adducts.…”

Proton pump inhibitors and histamine-2-receptor antagonists and pancreatic cancer risk: a nested case–control study

“…Gastric hypoacidity favours the overgrowth of bacteria in the stomach (Fried et al , 1994; Thorens et al , 1996), which results in the production of N-nitrosamines (Yeomans et al , 1995), although there is some evidence to the contrary (Vermeer et al , 2001). Pancreatic ductal adenocarcinomas have been seen to develop in mice and human pancreatic cells exposed to nitrosamines (Parsa et al , 1981; Parsa, 1987). PPI-/H 2 RA-related hypergastrinaemia may also contribute to pancreatic cancer carcinogenesis.…”

Induction of transformation and continuous cell lines from normal human mammary epithelial cells after exposure to benzo[a]pyrene.

“…However, transformation in vitro of human epithelial cells, the cell of origin of 85-90% of human cancers, has proved more difficult. Although epithelial cell cultures derived from numerous organs of rodent model systems have been neoplastically transformed by chemical carcinogens (6)(7)(8)(9)(10), there are few reports of carcinogen-induced transformation of human epithelial organ or cell cultures (11,12).…”