Pyrolysate mutagens

Morotomi, M. and Mutai, M., In vitro binding of potent mutagenic pyrolysates to intestinal bacteria, J. Natl. Cancer Inst, 77, 195-201, 1986. 

Kato, H. Kim, S.B. Hayase, F. Chuyen, N.V. Desmutagenicity of melanoidins against mutagenic pyrolysates. Agric. Biol. Chem. 1985, 49, 3093-3095. 

Sato T, Nagase H, Sato K, et al. 1994. Enhancement of the mutagenicity of amino acid pyrolysates by phthalate esters. Environ Mol Mut 24 325-331. 

The 3-amino-1 -mcthyl-5//-pyrido[4,3-b]indolc derivatives (31 Trp-P-1) and (32 Trp-P-2) were found as tryptophane pyrolysates in broiled fish and meat and in pyrolysates of protein and amino acids by Sugimura and coworkers198. These mutagens are heterocyclic amines and exhibit mutagenicity in the Ames test supplemented with S-9 mix198. The pyridoindole derivatives Trp-P-1 and Trp-P-2 are /V-hydroxylated at the exocyclic amino group to form proximate reactive compounds. 

Bhide. Mutagenicity of extracts of brown and black masheri, pyrolysed products of tobacco using short-term tests. Mutagenesis 1987 2(4) 263-266. 

NT136 Bhide, S. V., J. Kulkarni, U. J. Nair, B. Spiegelhalder, and R. Preussmann. Mutagenicity and carcinogenicity of masheri, a pyrolysed tobacco product, and its content of tobacco-specific nit-rosamines. lARC Sci Publ 1987 (84) 460-462. 

Kada, T., K. Morita, and T. Inoue. Anti-mutagenic action of vegetable factor(s) on the mutagenic principle of tryptophan pyrolysate. Mutat Res 1978 53 351-353. 

Arimoto, S., Nakano, N., Ohara, Y, Tanaka, K. Hayatsu, H. (1982) A solvent effect on the mutagenicity of tryptophan-pyrolysate mutagens in the SalmonellalraarwaaMan microsome assay. Mutat. Res., 102, 105-112... 

The first intimation that mutagens could be formed from natural food substances came from the laboratory of Sugimura, where it was found that mutagenic activity was found in smoke condensates or in DMSO extracts of the charred surface of fish and meat. This activity could not be accounted for by the amounts of BaP and PAH known to be present. Extracts of pyrolysates of various proteins and amino acids were also mutagenic (14). 

Several new facets of the chemical and physical behavior of mutagens isolated from food and pyrolysates have been noted recently. Trp-P-1, Trp-P-2, and Glu-P-1 are rapidly deaminated upon incubation with nitrite at acid pH (54). At pH 1.6, in 50 yM nitrite, the half lifetime of Trp-P-1 and Trp-P-2 is approximately 100 min, but less than 5 min for Glu-P-1. AdC is also deaminated in 1 mM sodium nitrite at pH less than four with the difference that longer incubation, for 1.5 h, leads to the formation of a directly mutagenic nitroso derivative (55). These reaction conditions approach those in the stomach (pH 1-2, 0-10 yM nitrite), but careful kinetic studies in vivo will be required... 

Mutagens Isolated from Pyrolysates of Amino Acids and Protein, and from Cooked Foods... 

DNA) (al-A R, L-type Ca2+ CH, DNA, 5HT2-R) [co-mutagenic, convulsant, cytoxic, genotoxic, motor depressant, DNA intercalator, sheep Tribulus staggers , vasorelaxant] from pyrolysate of Tryptophan (cooked food)... 

A special concern regarding the pyrolysis of Maillard polymers is the formation in this process of mutagenic compounds. Some of these compounds were isolated from pyrolysed food [5,6]. The formulas of several such compounds are shown below ... 

Besides the determination of major pyrolysis products for amino acids, a special issue is the formation of several mutagenic compounds (heterocyclic amines) during pyrolysis. These types of compounds were detected in traces in the pyrolysates of amino acids, and the finding is very important as the amino acids are components of proteins and are present in food. Some of these compounds isolated from pyrolysates performed at 550 C from several amino acids [5,6] are shown below ... 

Yl. Yamazoe, Y., Shimada, M., Kamataki, T., et al.. Microsomal activation of 2-amino-3-methyl imidazo[4,5-/]quinoline, a pyrolysate of sardine and beef extracts, to a mutagenic intermediate. Cancer Res. 43, 5763-5774 (1983). 

Yamazoe, Y., Ishii, K., Kamataki, T., Kato, R., and Sugimura, T., Isolation and characterization of active metabolites of tryptophan-pyrolysate mutagen, TRP-P-2, formed by rat liver microsomes, Chemico-Biol. Interact., 30, 125, 1980. 

Millon, H., Bur, H., and Turesly, R., Thermospray liquid chromatographic-mass spectrometric analysis of mutagenic substances present in tryptophan pyrolysates, J. Chromatogr., 394, 201-208, 1987. 

Of course, in 1971 when Patterson et al. offered this suggestion, the presence in amino acid pyrolysates of the so-called cooked food mutagens and the inordinately high mutagenicity of several of them were unknown. 

In 1977, Sugimura et al. (3829) reported the identihcation of the potent mutagens 3-amino-l-methyl-57/-pyrido[4,3- ] indole (coded Trp-P-2) and 3-amino-l,4-dimethyl-57/-pyrido[4,3-i ]indole (coded Trp-P-1) in pyrolysates from tryptophan. The next year, Yamamota et al. (4365a) identihed two additional highly mutagenic compounds in pyrolysates... 

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