Two food-borne heterocyclic amines: metabolism and DNA adduct formation of amino-alpha-carbolines.
The amino-alpha-carbolines 2-amino-9H-pyrido[2,3-b]indole (AalphaC) and 2-amino-3-methyl-9H-pyrido-[2,3-b]indole (MeAalphaC) are two mutagenic and carcinogenic heterocyclic amines formed during ordinary cooking. Amino-alpha-carbolines can be formed in model systems by pyrolyzing tryptophan or proteins of animal or vegetable origin, furthermore they are found in many cooked foods, such as fish, meat, and chicken. The specific mutagenicity of the amino-alpha-carbolines are lower in the Ames Salmonella assay than other heterocyclic amines, but in rodent studies the carcinogenicity of the amino-alpha-carbolines are comparable to other heterocyclic amines. The metabolic pathways of the amino-alpha-carbolines have been studied in vitro and in vivo, and the detoxified phase I and phase II metabolites characterized and quantified. The metabolic activation of the amino-alpha-carbolines and the formation of DNA-adducts have also been studied. Characteristic for the amino-alpha-carbolines are that relatively large amounts of these compounds in rat and human hepatic microsomes are activated to potent carcinogenic compounds compared with other heterocyclic amines, but further in vivo studies of the amino-alpha-carbolines are needed to highlight these indications. In this review, the main characteristics with focus on the metabolism and the DNA-adduct formation of the amino-alpha-carbolines are described and compared with other heterocyclic amines.
Frederiksen
Hanne
H
Department of Toxicology and Risk Assessment, Danish Institute for Food and Veterinary Research, Søborg, Denmark. haf@dfvf.dk
D000588:Amines; D000818:Animals; D002243:Carbolines / Q000378:metabolism*; D002273:Carcinogens; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D018736:DNA Adducts / Q000378:metabolism*; D005504:Food Analysis; D006571:Heterocyclic Compounds; D006358:Hot Temperature; D006801:Humans; D008460:Meat / Q000032:analysis; D008862:Microsomes, Liver / Q000201:enzymology; D009153:Mutagens; D051381:Rats
D000588:Amines; D002243:Carbolines; D002273:Carcinogens; D018736:DNA Adducts; D006571:Heterocyclic Compounds; D009153:Mutagens; C017821:2-amino-3-methyl-9H-pyrido(2,3-b)indole; D003577:Cytochrome P-450 Enzyme System; C017822:2-amino-9H-pyrido(2,3-b)indole