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Inhibitory effect of Browning reaction products and phenolic compounds on carcinogen-induced mutagenesis

University of British Columbia

Chemical carcinogens are highly reactive electrophilic substances capable of interacting with nucleophilic sites indiscriminately. The use of nucleophilic trapping agents that react with electrophiles could thus provide possible protection for critical cellular targets against the action of chemical carcinogens. It was on the basis of this general concept that substances in the present study were examined for possible inhibitory activities against carcinogen-induced mutagenesis. Non-enzymatic browning reactions occur in virutually all heated food stuffs. Phenolic compounds are also widely distributed in plants and are consequently present in many foods. Antimutagenic activity of two non-enzymatic browning reaction products (caramelized sucrose and lysine-fructose Maillard reaction products) and several phenolic compounds were determined in the present study. At non-toxic concentrations, the two browning reaction products and three phenolic compounds (gallic acid, caffeic acid and chlorogenic acid) significantly suppressed the mutagenicity of the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in Salmonella typhimum-um strain TA 1535 and Sacchavomyces cerevis-iae strain XV185-14C. Interaction between phenolic compounds and MNNG was also studied in a cell-free system. The amount of MNNG, detected by a colorimetric method, following its incubation with phenolic compounds decreased substantially compared to that in the untreated MNNG controls. The results are consistent with the assumption that phenolic compounds scavenged reactive electrophilic MNNG degradation products thereby preventing their action on critical cellular targets. The two browning reaction products and seven phenolic compounds (tannic acid, gallic acid, caffeic acid, chlorogenic acid, salicylic acid, p-hydroxybenzoic acid and dopamine) also reduced the mutagenicity of the precarcinogen, aflatoxin B₁ (AFB₁), when assayed on Salmonella typh-imurium strain TA 98 in the presence of a rat liver microsomal activation system. The effect of phenolic compounds on the activation of AFB^ by rat liver microsomes was also studied by high-pressure liquid chromatography (HPLC). The results from the HPLC analysis suggested that one mechanism whereby the phenolic, compounds suppressed the mutagenic activity of AFB₁ is by interfering with its metabolic activation. However, the possibility remains that part of the antimutagenic activity observed may be due to interactions between the phenolic compounds and the reactive metabolite(s) of AFB₁. The present study does not permit an assessment of the relative contribution of the two mechanisms of antimutagenic action.

Text

2010-04-20

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http://hdl.handle.net/2429/23920

Medical Genetics

University of British Columbia

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