3-amino-1-methyl-5h-pyrido(4-3-b)indole and harman

Topics: Animals; Breast Neoplasms; Carbolines; Carcinogens, Environmental; Cattle; Colonic Neoplasms; Cooking; Food; Harmine; Head and Neck Neoplasms; Humans; Imidazoles; Male; Meat; Mutagens; Neoplasms; Nitrates; Nitrites; Nitrosamines; Prostatic Neoplasms

Heat processing of muscle foods gives rise to the formation of mutagenic and carcinogenic heterocyclic amines, often at ng/g levels. A gas chromatographic-mass spectrometric (GC-MS) technique was introduced for the analysis of nonpolar heterocyclic amines in common cooked meats, pan residues, and meat extracts after solid-phase extraction. The mutagenic heterocyclic amines 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-9H-pyrido[2,3-b]indole (A alpha C) and 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C) were identified in several samples in amounts up to 8 ng/g. Also the comutagenic substances 1-methyl-9H-pyrido [3,4-b]indole (harman) and 9H-pyrido[3,4-b]indole (norharman) were detected in the samples in amounts up to almost 200 ng/g. The GC-MS method can be applied without derivatisation of the sample. The technique offers high chromatographic efficiency, yielding detection limits for pure references in the range 0.1-2 ng per injection.

Topics: Amines; Animals; Carbolines; Carcinogens; Cooking; Gas Chromatography-Mass Spectrometry; Harmine; Heterocyclic Compounds; Hot Temperature; Meat; Meat Products; Mutagens; Reindeer; Surface Properties; Swine

beta-Carbolines, harman (1-methyl-9H-pyrido[3,4-b]indole) and norharman (9H-pyrido[3,4-b]indole) and gamma-carbolines, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-4-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), are present in cooked foods and cigarette smoke. We studied the effects of these heterocyclic amines on the activity of DNA topoisomerases. Trp-P-1 and Trp-P-2 inhibited topoisomerase I (topo I) activity with ED50 values of 1.48 and 1.55 micrograms/ml, respectively, in a relaxation assay. Harman and norharman inhibited topo I activity but with much higher ED50 values, 23.8 and 34.4 micrograms/ml, respectively. Trp-P-1 and Trp-P-2 also inhibited topoisomerase II (topo II) activity at about 50 micrograms/ml, in a decatenation assay. Harman and norharman showed a much lower inhibitory effect on topo II activity. None of these compounds stabilized the cleavable complex mediated by topo II. Trp-P-1 and Trp-P-2 intercalated into DNA at concentrations inhibitory to topoisomerases. We considered that the intercalation with DNA and the inhibition of DNA topoisomerases by heterocyclic amines might be partly related to their inhibition of DNA excision repair and their enhancing effect on UV- or chemically induced mutagenic activity.

Topics: Breast Neoplasms; Carbolines; Carcinoma, Small Cell; Cell Line; Enzyme Inhibitors; Female; Harmine; Humans; Kinetics; Mutagens; Topoisomerase I Inhibitors; Topoisomerase II Inhibitors; Tumor Cells, Cultured