Abstract
Lifestyle, especially diet, significantly impacts cancer development. Sugimura, T. et al. discovered that grilled fish smoke and charred parts are highly mutagenic in Salmonella typhimurium. They identified two novel mutagenic heterocyclic amines (HCAs), 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and its derivative, Trp-P-2, from tryptophan pyrolysate. Published in Proc. Jpn. Acad. (53, 58-61, 1977), their findings initiated the identification of over 10 mutagenic HCAs in cooked foods, most of them newly registered. These 10 HCAs were demonstrated to induce cancers in organs including the liver, colon, breast, and prostate in mice and rats. HCAs are metabolized primarily by CYP1A2 to hydroxyamino derivatives. Their ester forms then adduct at guanine bases, altering genes such as Apc and β-catenin. Quantification of HCAs in cooked foods and human samples, along with epidemiological observations, suggests HCAs likely contribute to human cancers.