Possible roles of excess tryptophan metabolites in cancer.
Tryptophan is metabolized through serotonin, indole, and kynurenine (KN) pathways. Uptake of an excess amount of tryptophan accompanied with vitamin B6 deficiency may result in the accumulation of higher concentrations of metabolites mainly from the KN pathways in the bladder. These metabolites could interact with nitrite to become mutagenic nitrosamines. They could be a promoter in the initiator-promoter model of carcinogenesis. They produced bladder cancer when implanted in the bladder. They also interact with transition metals copper or iron to form reactive radicals or reactive oxygen species (ROS). Some metabolites, 3-hydroxy-anthranilic acid, were autooxidized to mutagenic cinnabarinic and anthranilyl radical intermediates. These radical intermediates could also be ligands that interact with aryl hydrocarbon receptor (AhR) and induce xenobiotic metabolizing enzymes (XMEs) to metabolize contaminated carcinogens. When tryptophan is exposed to either visible or UV light, a photoproduct of 6-formylindolo[3,2b]-carbazole is formed, which has a very high affinity for the AhR that plays a role in carcinogenesis. This review gives an insight into various mechanisms through which tryptophan metabolites cause carcinogenesis. It could be concluded that tryptophan metabolites play a complementary role in promoting carcinogenesis along with carcinogens like aflatoxin, CCl(4) , 2-acetylaminofluorene, 4-aminobiphenyl, 2-naphthylamine, or N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide. The underlying mechanisms could be their autoxidation, exposure to either visible or UV light, interaction with nitrite or transition metals to form reactive intermediates, serving as ligands to interact with an AhR that is known to play a role in carcinogenesis through induction of XMEs. Further research is warranted.Environ.
Chung
King-Thom
KT
Department of Biology, The University of Memphis, Memphis, Tennessee, USA. kchung@memphis.edu
Gadupudi
Gopi S
GS
D000818:Animals; D002273:Carcinogens / Q000737:chemistry / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects; D004285:Dogs; D006801:Humans; D007737:Kynurenine / Q000378:metabolism; D008113:Liver Neoplasms / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D051379:Mice; D009153:Mutagens / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000378:metabolism
D002273:Carcinogens; D009153:Mutagens; D012701:Serotonin; D007737:Kynurenine; D014364:Tryptophan