HUMAN EXPOSURE TO MUTAGENIC CARCINOGENIC HETEROCYCLIC AMINES AND COMUTAGENIC BETA-CARBOLINES/

Various kinds of mutagenic and carcinogenic heterocyclic amines (HCAs) are produced by heating protein-rich foods, such as meat and fish. To evaluate the risk of these HCAs in terms of human cancer development, exposure levels must be measured. We therefore analyzed their amounts in various kinds of cooked foods and in urine samples of healthy volu nteers living in Tokyo. Based on the obtained quantitative data, daily exposure levels to 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeI Qx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) were ca lculated to be 0.3-3.9 and 0.005-0.3 mu g per person, respectively, Mo reover, human DNA samples were analyzed with the P-32-postlabeling met hod, and colon, rectum and kidney tissues were found to contain an add uct spot corresponding to the standard 5'-pdG-C8-MeIQx by TLC and HPLC , at levels of 14, 18 and 1.8 per 10(10) nucleotides, respectively. Th e beta-carboline compound, norharman, is produced by heating L-tryptop han, and is known to be present in cooked foods and in cigarette smoke at higher levels than mutagenic and carcinogenic HCAs. While norharma n is not itself mutagenic to Salmonella, it does become mutagenic to S . typhimurium TA98 with S9 mix in the presence of non-mutagenic aromat ic amines like aniline and o-toluidine. When we examined whether DNA a dducts are formed in the DNA of S. typhimurium TA98 by treatment with norharman and aromatic amines using P-32-postlabeling analysis, DNA ad duct formation by norharman with aromatic amines was found to be relat ed to the appearance of mutagenicity by norharman with aromatic amines .