Use of transgenic and mutant animal models in the study of heterocyclic amine-induced mutagenesis and carcinogenesis.
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.
Dashwood
Roderick H
RH
Department of Environmental & Molecular Toxicology, and Linus Pauling Institute, Oregon State University, Corvallis, OR 97331-6512, USA. Rod.Dashwood@oregonstate.edu
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
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