The objective of this proposal is to investigate the role that elevated dietary tryptophan may play in promotion during the course of liver tumorigenesis. Based upon experimental studies by others and by us, L-tryptophan has been demonstrated to enhance liver carcinogenesis induced by selected hepatocarcinogens. We plan to focus our attention on how elevated dietary tryptophan acts as a promoter. In view of previous findings by others and by us that L-tryptophan has unique actions on the control of hepatic polyribosomes and protien synthesis, we plan to explore whether some of these effects are influential during promotion. We hypothesize that L-tryptophan may act as a promoter in liver carcinogenesis by stimulating nucleocytoplasmic translocation of mRNA in the liver. Such stimulation directed after the process of initiation (as by administering diethylnitrosamine shortly after subtotal hepatectomy) may lead toward the emergence of more Gamma-glutamyltranspeptidase positive hepatocytes and ultimately more hepatocellular carcinomas. Studies relating to this process and alterations in nuclear membranes, specifically proteins (glycoproteins such as lamin B), are planned. In addition, we plan to investigate other possible ways tryptophan may act as promoter, such as possibly by affecting cell necrosis and/or cell proliferation, by diminishing liver glutathione levels, or by reacting in the gastrointestinal tract with nitrites to form carcinogenic compounds.
NIH ExPorter
NIH ExPorter