Carcinogenicity in Mice and Rats of Heterocyclic Amines in Cooked Foods

Abstract

JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact support@jstor.org.. The National Institute of Environmental Health Sciences (NIEHS) andBrogan & Partners are collaborating with JSTOR to digitize, preserve and extend access to Environmental Health Perspectives. Carcinogenicities of mutagenic heterocyclic amines in cooked foods have been tested in CDFx mice and F344 rats of both sexes. Eight heterocyclic amines?Trp-P-1,Trp-P-2, Glu-P-1, Glu-P-2, MeAaC, AaC, IQ, and MelQ?were given to mice and/or rats at 0.02 to 0.08% in the diet continuously. In mice, all heterocyclic amines tested were demonstrated to be carcinogenic. Hepatocellular carcinomas were induced in a high incidence in all groups treated with heterocyclic amines. Hemangioendothelial sarcomas were also induced by Glu-P-1, Glu-P-2, MeAaC, and AaC. Most hemangioendothelial sarcomas were located in the interscapular brown adipose tissue. In mice given IQ, forestomach and lung tumors were also observed in a high incidence. Carcinogenicity tests on MelQ are ongoing, and interim data by week 83 show that MelQ also induces forestomach tumors in addition to liver tumors.In rats, hepatocellular carcinomas were induced by Trp-P-1, Glu-P-1, Glu-P-2, and IQ. In rats given Glu-P-1, Glu-P-2, and IQ, adenocarcinomas in the small and large intestines, squamous cell carcinomas in the Zymbal gland and clitoral gland were also observed in a high incidence.

Updated Histologic Classification of Adenomas and Carcinomas in the Colon of Carcinogen-treated Sprague-Dawley Rats

“…Several histological classifications of carcinogen-induced colonic adenomas and carcinomas in rats have been proposed (5)(6)(7)(8)(9)(10)(11)(12)(13)). The present study shows that SD rats treated with the colonotropic carcinogen DMH develop supplementary histological neoplastic phenotypes such as traditional (serrated and microtubular) adenomas, GALT-associated adenomas, villous carcinomas, serrated carcinomas, microtubular carcinomas, GALT-associated tubular carcinomas and GALTassociated signet-ring cell carcinomas, in addition to the colonic tumors in rodents reported in the literature (5)(6)(7)(8)(9)(10)(11)(12)(13).…”

“…Several of the histological phenotypes reported here are not included in any of the current classifications of carcinogen-induced colon neoplasias in rodents (5)(6)(7)(8)(9)(10)(11)(12)(13). The purpose of studying colonic carcinogenesis is to explore whether the histological changes found in rodents are similar to those evolving during colorectal carcinogenesis in humans.…”

“…In more recent years, several histological classifications of experimentally-induced colonic adenomas in rats have been proposed (5)(6)(7)(8)(9)(10)(11)(12)(13). Some researchers classify adenomas into tubular, villous and a mixed phenotype and tubulo-villous, others into adenomas with mild, moderate and severe dysplasia, and a third group regard adenomas as only those exhibiting severe dysplasia.…”

“…Some researchers classify adenomas into tubular, villous and a mixed phenotype and tubulo-villous, others into adenomas with mild, moderate and severe dysplasia, and a third group regard adenomas as only those exhibiting severe dysplasia. Similarly, some authors classify invasive carcinomas into well-, moderately and poorly differentiated, and signet-ring cell carcinomas; others into tubular, mucinous, signet-ring cell and undifferentiated; and by a third group into scirrhous, tubular, papillary, tubular-papillary, mucinous, signetring, solid, undifferentiated, and mixed types (5)(6)(7)(8)(9)(10)(11)(12)(13). In contrast, Deschner (14), Maskens (15) and, more recently, Ward and Treuting (16) have asserted that adenocarcinomas often develop de novo, and not from adenomas, therefore, adenomas were not histologically classified.…”

“…Despite the disparate classifications of colonic neoplasias in rodents, the general view has been that colonic carcinomas evolve from conventional (tubular, tubulo-villous or villous) adenomas (5)(6)(7)(8)(9)(10)(11)(12)(13). However, recent studies have disclosed additional histological phenotypes of colonic adenomas and carcinomas in DMH-treated Sprague-Dawley (SD) rats (17)(18)(19) as follows.…”