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Use of Transgenic and Mutant Animal Models in the Study of Heterocyclic Amine-induced Mutagenesis and Carcinogenesis

  • Dashwood, Roderick H. (Department of Environmental & Molecular Toxicology, and Linus Pauling Institute, Oregon State University)
  • Published : 2003.01.31
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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 $gpt{\Delta}$ transgenics, $XPA^{-/-}$, $XPC^{-/-}$, $Msh2^{+/-}$, $Msh2^{-/-}$ and $p53^{+/-}$ knock-outs, Apc mutant mice ($Apc^{{\Delta}716}$, $Apc^{1638N}$, $Apc^{min}$), and $A33^{{\Delta}N{\beta}-cat}$ 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.

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References

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