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

摘要

Heterocyclic amines (HCAs) are potent mutagens generated during the cooking of meat and fish, and several of these compounds produce tumors in conventional experimental animal. 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△ transgenics, XPA~(-/-), XPC~(-/-), Msh2~(-/-), Msh2~(-/-) and p53~(-/-) knock-outs, Apc mutant mice (APc~(△716), Apc~(1638N), Apc~(min)) and A33~(△Nβ-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.