Experimental pancreatic cancer: role of species, sex and diet.
Pancreatic cancer has been experimentally induced in rodents by chemical carcinogens that have been used to establish "animal models" for pancreatic carcinogenesis. Recent work with transgenic mice provided a new model in which a dominantly expressed oncogene is transmitted in the germ cell line of homozygous strains. Carcinogens are not equally effective in all species and the histologic type of carcinoma that develops is strongly influenced by the species. Carcinomas that develop in rats and mice are predominantly acinar cell type. In contrast, hamsters characteristically develop duct-like carcinomas. The histologic type of carcinoma in hamsters resembles more closely the majority of carcinomas in the human pancreas than is the case in the rat or mouse. Studies in rats and guinea pigs have demonstrated that duct-like and undifferentiated carcinomas, as well as acinar cell carcinomas, can arise from acinar cells. Thus, the relative importance of ductal cells, centroacinar cells, acinar cells and putative stem cells in the origin of pancreatic carcinomas remains to be determined. In most rat models, males have developed a higher incidence rate of pancreatic cancers than females. Experimental evidence shows that testosterone promotes and estrogen inhibits the growth of preneoplastic lesions and cancers in the rat pancreas. Dietary composition and additives influence carcinogenesis in the pancreas. High fat diets promote carcinogenesis in rats and hamsters, and dietary trypsin inhibitors promote in rats. Other dietary additives such as retinoids and antioxidants have inhibited carcinogenesis in the animal models.
Longnecker
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Department of Pathology, Dartmouth Medical School Hanover, NH 03756.
D000818:Animals; D002273:Carcinogens; D006224:Cricetinae; D004032:Diet / Q000009:adverse effects*; D004041:Dietary Fats / Q000009:adverse effects; D005260:Female; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental; D010190:Pancreatic Neoplasms / Q000209:etiology* / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D012176:Retinoids / Q000494:pharmacology; D012737:Sex Factors
D002273:Carcinogens; D004041:Dietary Fats; D012176:Retinoids