Heterocyclic Amines (HCA)

Heterocyclic amines (HCAs) contain at least one heterocyclic ring (with atoms of at least 2 different elements) and one amine group, attached to the heterocyclic ring. Major groups of HCAs are beta-Carbolines, Pyrrolidines, Pyrroles (in Hb and vitamin B12), Pyridines (vitamin B3 and B6) and Pyrimidines (vitamin B1), including Purines (adenine, guanine).

Many HCA are harmless, or even beneficial (eg vitamins), whereas others, created by cooking or burning, may cause cancer.

Mutagenic HCA in cigarette smoke

The following HCA are a few of the HCA found in cigarette smoke:

• Trp-P-1 [1]
• Trp-P-2 [2]
• Glu-P-1 [3]
• A alpha C [4]
• MeA alpha C [5]
• PhIP [6]

But exactly the same HCA are also found in cooked foods:

• Trp-P-1 [7][8]
• Trp-P-2 [9][10]
• Glu-P-1 [11]
• Glu-P-2 ,,
• A alpha C ..
• MeA alpha C ..
• PhIP

Mutagenic HCA in cooked foods

HCAs form when amino acids and creatine react at high cooking temperatures. Antioxidants inhibit HCA formation [12]. Enzymes in the human body activate those HCAs: HCAs are oxidized to hydroxyamino derivatives by cytochrome P450s, and further converted to ester forms by acetyltransferase and sulfotransferase. Eventually, they produce DNA adducts through the formation of N-C bonds at guanine bases [13], which actually exist in human tissues, and may be involved in human cancer development [14] Adding PhIP to the diet at a concentration of 400 ppm (parts per million) for 1 year induced carcinomas in 47% of female rats. 100 ppm of PhIP for 2 years yielded the same incidence. [15]

Mutagenic HCAs in cooked foods

• 2-amino-3-methylimidazo[4,5-f]quinoline (IQ; in broiled sardines, cooked beef, fried fish) [16]
• 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ; in fried fish) [17][18][19]
• 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx; in various cooked foods) [20]
• 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP; in cooked meat and fish) [21][22]
• 2-amino-1-methyl-6-(4-hydroxyphenyl)imidazo[4,5-b]pyridine (4'-OH-PhIP; in broiled beef) [23] (creatine + tyrosine + glucose)
• 2-amino-n,n-dimethylimidazopyridine (DMIP) [24]
• 2-amino-n,n,n-trimethylimidazopyridine (TMIP) [25]
• 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx; in fried fish [26] and beef extract [27]}
• 2-amino-3,7,8-trimethylimidazo[4,5-f]quinoxaline (7,8-DiMeIQx; in roasted eel) [28] (creatinine + glycine + glucose[29])
• 2-amino-4-hydroxymethyl-3,8-dimethylimidazo[4,5-g]quinoxaline (4-CH2OH-8-MeIQx; in beef extract) [30]
• 2-amino-1,7,9-trimethylimidazo[4,5-g]quinoxaline (7,9-DiMeIgQx++ +; in beef extract) [31]

• 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1)
• 2-aminodipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2)
• 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1; a gamma-carboline)
• 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2; a gamma-carboline)
• 2-amino-9H-pyrido[2,3-b]indole (A alpha C)
• 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C)

Non-mutagens in cooked food converted to mutagens in the body

Cooked foods contain various beta-carbolines (produced by heating L-tryptophan [32]), such as harman and norharman. [33] Mutagenic aminophenylnorharman (APNH) is formed from non-mutagenic norharman and aniline. [34][35]

beta-Carbolines in cooked foods

• 1-methyl-9H-pyrido[3,4-b]indole (harman)
• 9H-pyrido[3,4-b]indole (norharman)