Presence of carcinogenic heterocyclic amines in urine of healthy volunteers eating normal diet, but not of inpatients receiving parenteral alimentation

Abstract

For estimation of human exposures to carcinogenic heterocyclic amines, the amounts of four compounds, 3-amino-1, 4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), in human urine were measured. Twenty-four hour urine specimens were collected from ten healthy volunteers eating normal diet (five males and five females) and three inpatients (two males and a female) receiving parenteral alimentation, and the levels of the four heterocyclic amines were measured by HPLC after partial purification by treatment with blue cotton and ion exchange column chromatography. Trp-P-1, Trp-P-2, PhIP and MeIQx were detected in the 24 h urine samples of all healthy volunteers at levels of 0.04-1.43 ng, 0.03-0.68 ng, 0.12-1.97 ng and 11-47 ng respectively. As 1.8-4.9% of an oral dose of MeIQx is reported to be excreted unchanged in the urine, the daily exposure of humans to MeIQx was estimated to be 0.2-2.6 micrograms/person. The four heterocyclic amines were not detected in the urine of parenterally fed inpatients. These results indicate that humans are continually exposed to carcinogenic heterocyclic amines in food, and these compounds may not be formed endogenously.

Detection of Aminophenylnorharman, a Possible Endogenous Mutagenic and Carcinogenic Compound, in Human Urine Samples

“…The level of APNH in human urine samples was much lower than found earlier for MeIQx, but comparable with that for 3-amino-1,4-dimethyl-5H-pyrido [4,3-b]indole (Trp-P-1; ref. 13). However, APNH is a more potent carcinogen than Trp-P-1 and MeIQx (10,28), so that the risk of human cancer might be similar.…”

“…[ 2 H 4 ]APNH was used as an internal standard and added to each urine sample before blue rayon treatment. The urine sample was treated with 6 g blue rayon for three times, which was then washed with water, and adsorbed materials were extracted with 1.2 liters of methanol/ammonia water (50:1, v/v), as previously reported (13). The extracts were evaporated to dryness, and the residues were dissolved in methanol and further purified by high-performance liquid chromatography (HPLC).…”

“…Norharman has been reported to be present at much higher levels than mutagenic and carcinogenic heterocyclic amines, such as 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) and MeIQx, in cigarette smoke condensate and cooked foodstuffs and indeed was detected in human urine samples at levels much higher than for PhIP or MeIQx (12,13). Moreover, aniline is not only used in various ways as an industrial raw material but also ubiquitously present in cigarette smoke condensate and some vegetables and has also been detected in human urine and breast milk (14)(15)(16)(17).…”

Polymorphisms for Aromatic Amine Metabolism in Humans: Relevance for Human Carcinogenesis

“…During the cooking process, pyrolysis of meat liquids can result in the formation of mutagenic and carcinogenic heterocyclic amines (14), such as 2-amino-3-methylimidazo[4,5-J]quinoline (IQ), 2-amino-3,8-dimethylimidazo-[4,5-flquinoxaline (MeIQx), 2-amino-1-methyl-6-phenyHmidazo [4,5-b]pyridine (PhIP), and 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1). Several of these aromatic amines are known to induce tumors in experimental animals in a variety of tissues, notably the liver and intestine (15); and they have also been detected in urine of individuals who consume a normal, meat-containing diet (16). Their metabolic activation pathways have been extensively studied in rodents, and we have recently shown that human liver and colon tissues possess comparable enzyme systems (17).…”

Inter-Individual Variation in the Metabolic Activation of Heterocyclic Amines and Susceptibility to Prostate Cancer

“…The positive correlation between meat consumption and cancer incidence such as those of the stomach (5), prostate (6), breast (7,8), lung (9) in human populations (10) along with carcinogenicity to rats and mice (11)(12)(13) of these compounds suggest that they may be an important factor in diet-related human cancers. The critical step in HCA bioactivation is catalyzed by the CYP mediated A/-hydroxylation, forming its major metabolite, A/-hydroxy HCA (14)(15)(16)(17). The presence of CYP1A2, CYP1A1 and CYP1B1 mRNA in the human prostate has been reported (18).…”