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 volunteers living in Tokyo. Based on the obtained quantitative data, daily exposure levels to 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) were calculated to be 0.3-3.9 and 0.005-0.3 microgram per person, respectively. Moreover, human DNA samples were analyzed with the 32P-postlabeling method, and colon, rectum and kidney tissues were found to contain an adduct 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. The beta-carboline compound, norharman, is produced by heating L-tryptophan, and is known to be present in cooked foods and in cigarette smoke at higher levels than mutagenic and carcinogenic HCAs. While norharman is not itself mutagenic to Salmonella, it does become mutagenic to S. typhimurium TA98 with S9 mix in the presence of non-mutagenic aromatic amines like aniline and o-toluidine. When we examined whether DNA adducts are formed in the DNA of S. typhimurium TA98 by treatment with norharman and aromatic amines using 32P-postlabeling analysis, DNA adduct formation by norharman with aromatic amines was found to be related to the appearance of mutagenicity by norharman with aromatic amines.
Wakabayashi
K
K
Biochemistry Division, National Cancer Center Research Institute, Tokyo, Japan.
Totsuka
Y
Y
Fukutome
K
K
Oguri
A
A
Ushiyama
H
H
Sugimura
T
T
D000814:Aniline Compounds / Q000378:metabolism; D002243:Carbolines / Q000008:administration & dosage* / Q000032:analysis; D003106:Colon; D018736:DNA Adducts / Q000032:analysis*; D004032:Diet; D004781:Environmental Exposure; D005260:Female; D006247:Harmine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000032:analysis* / Q000652:urine; D008297:Male; D008460:Meat; D009152:Mutagenicity Tests; D011810:Quinoxalines / Q000032:analysis* / Q000652:urine; D012486:Salmonella typhimurium / Q000187:drug effects; D014052:Toluidines / Q000378:metabolism
D000814:Aniline Compounds; D002243:Carbolines; D018736:DNA Adducts; D007093:Imidazoles; D011810:Quinoxalines; D014052:Toluidines; D006247:Harmine; C019133:3-amino-1-methyl-5H-pyrido(4,3-b)indole; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; C010262:norharman; C023650:aniline