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 (Apc(Delta716), Apc(1638N) Apc(min)), and A33(DeltaNbeta-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.