title: Use of transgenic and mutant animal models in the study of heterocyclic amine-induced mutagenesis and carcinogenesis.
abstract: Heterocyclic amines (HCAs) are potent mutagens generated during the cooking of meat and fish, and several of these compounds produce tumors in conventional experimental animals. During the past 5 years or so, HCAs have been tested in a number of novel in vivo murine models, including the following: lacZ, lacI, cII, c-myc/lacZ, rpsL, and gptDelta. transgenics, XPA-/-, XPC-/-, Msh2+/-, Msh2-/- and p53+/- knock-outs, Apc mutant mice (ApcDelta716, Apc1638N, Apcmin), and A33DeltaNbeta-cat knock-in mice. Several of these models have provided insights into the mutation spectra induced in vivo by HCAs in target and non-target organs for tumorigenesis, as well as demonstrating enhanced susceptibility to HCA-induced tumors and preneoplastic lesions. This review describes several of the more recent reports in which novel animal models were used to examine HCA-induced mutagenesis and carcinogenesis in vivo, including a number of studies which assessed the inhibitory activities of chemopreventive agents such as 1,2-dithiole-3-thione, conjugated linoleic acids, tea, curcumin, chlorophyllin-chitosan, and sulindac.
authors.affiliation: Department of Environmental & Molecular Toxicology, and Linus Pauling Institute, Oregon State University, Corvallis, OR 97331-6512, USA. Rod.Dashwood@oregonstate.edu
authors.forename: Roderick H
authors.initials: RH
authors.lastname: Dashwood
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D000588:Amines / Q000633:toxicity; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced*; D018890:Chemoprevention; D004268:DNA-Binding Proteins / Q000235:genetics; D004195:Disease Models, Animal; D006571:Heterocyclic Compounds / Q000633:toxicity*; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D051718:MutS Homolog 2 Protein; D016296:Mutagenesis; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012269:Ribosomal Proteins / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D051760:Xeroderma Pigmentosum Group A Protein; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D000588:Amines; D004268:DNA-Binding Proteins; D006571:Heterocyclic Compounds; D011518:Proto-Oncogene Proteins; D012269:Ribosomal Proteins; D016159:Tumor Suppressor Protein p53; D051760:Xeroderma Pigmentosum Group A Protein; C497315:Xpa protein, mouse; C034212:ribosomal protein S12; D001616:beta-Galactosidase; C497173:Msh2 protein, mouse; D051718:MutS Homolog 2 Protein