Enzymatic and nonenzymatic browning reactions of amino acids and proteins with carbohydrates, oxidized lipids, and oxidized phenols cause deterioration of food during storage and processing. The loss in nutritional quality and potentially in safety is attributed to destruction of essential amino acids, decrease in digestibility, inhibition of proteolytic and glycolytic enzymes, interaction with metal ions, and formation of antinutritional and toxic compounds. Studies in this area include influence of damage to essential amino acids on nutrition and food safety, nutritional damage as a function of processing conditions, and simultaneous formation of deleterious and beneficial compounds. These compounds include kidney-damaging Maillard reaction products, mutagens, carcinogens, antimutagens, antioxidants, antibiotics, and antiallergens. This overview covers the formation, nutrition, and safety of glycated proteins, characterized browning products, and heterocyclic amines. Possible approaches to inhibiting browning reactions and preventing adverse effects of browning during food processing and food consumption, including protection against adverse effects of heterocyclic amines by N-acetylcysteine, caffeine, chlorophyll, conjugated linoleic acid, lignin, and tea extracts, are also described. This research subject covers a complex relationship of the chemistry, biology, and pathology of browning products and the impact on human nutrition and health. Future study should differentiate antinutritional and toxicological relationships, define individual and combined potencies of browning products, and develop means to prevent the formation and to minimize the adverse manifestations of the most antinutritional and toxic compounds. Such studies should lead to better and safer foods and improved human health.

http://nfscfaculty.tamu.edu/talcott/courses/FSTC605/Papers%20Reviewed/Food%20Browning.pdf

Food browning and its prevention: an overview

Digestion, absorption, and cancer preventative activity of dietary chlorophyll derivatives

Three major factors for human carcinogenesis are (i) cigarette smoking, (ii) infection and inflammation and (iii) nutrition and dietary factors. Nutrition and dietary factors include two categories, namely genotoxic agents and constituents including tumor promotion-associated phenomena. This article first describes the genotoxic agents as microcomponents. These are mutagens/carcinogens in cooked food, fungal products, plant and mushroom substance, and nitrite-related materials, polycyclic aromatic hydrocarbons and oxidative agents. Emphasis has been given to heterocyclic amines (HCAs) to which humans are continuously exposed in an ordinary lifestyle. HCAs in food are mainly produced from creatin(in)e, sugar and from amino acids in meat (upon heating). They are imidazoquinoline and imidazoquinoxaline derivatives and phenylimidazopyridine. HCAs are pluripotent in producing cancers in various organs including breast, colon and prostate. Discussion is also given to plant flavonoids which are mutagenic but not carcinogenic. As a macrocomponent, overintake of total calories, fat and sodium chloride is discussed from the viewpoint of the increase of genetic alterations in tissues and of tumor promotion-associated issues. Studies of nutrition and dietary condition will eventually lead us to cancer prevention, namely delay of onset of cancer to the late phase of human life, which is called 'natural-end cancer' (Tenju-gann).

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Nutrition and dietary carcinogens

In vitro antioxidant and antimutagenic activity of dietary chlorophyll derivatives was assessed. Anti- oxidant activity was determined by the ability of each compound to scavenge the long-lived free radicals 1,1- diphenyl-2-picrylhydrazyl (DPPH · ) and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS ·+ ). Antimu- tagenic activity was assayed with a modified microscreen bacterial reverse mutagenicity assay using Salmonella typhimurium TA100 and benzo(a)pyrene as the tester strain and mutagen respectively. Derivatives of chlorophyll a were found to be more effective radical quenchers than those of chlorophyll b. Furthermore, metal-free derivatives such as chlorins, pheophytins, and pyropheophytins exhibited significantly lower antiradical capacity than metallo- derivatives such as Mg-chlorophylls, Zn-pheophytins, Zn-pyropheophytins, Cu-pheophytin a, and Cu-chlorophyllins. Both metal-free and metallo-chlorophyll derivatives demonstrated similar dose-dependent inhibitory activity against B(a)P induced mutagenesis. These results demonstrate that dietary chlorophyll derivatives prevalent in both fresh and processed foods and dietary supplements have antioxidant and antimutagenic activities.

Antioxidant and Antimutagenic Activity of Dietary Chlorophyll Derivatives Determined by Radical Scavenging and Bacterial Reverse Mutagenesis Assays

There is growing interest in the potential health benefits of tea, including the antimutagenic properties. Four varieties of white tea, which represent the least processed form of tea, were shown to have marked antimutagenic activity in the Salmonella assay, particularly in the presence of S9. The most active of these teas, Exotica China white tea, was significantly more effective than Premium green tea (Dragonwell special grade) against 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and four other heterocyclic amine mutagens, namely 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethyl-3H-imidazo[4,5-f]quinoxaline (4,8-DiMeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2). Mechanism studies were performed using rat liver S9 in assays for methoxyresorufin O-demethylase (MROD), a marker for the enzyme cytochrome P4501A2 that activates heterocyclic amines, as well as Salmonella assays with the direct-acting mutagen 2-hydroxyamino-3-methylimidazo[4,5-f]quinoline (N-hydroxy-IQ). White tea at low concentrations in the assay inhibited MROD activity, and attenuated the mutagenic activity of N-hydroxy-IQ in the absence of S9. Nine of the major constituents found in green tea also were detected in white tea, including high levels of epigallocatechin-3-gallate (EGCG) and several other polyphenols. When these major constituents were mixed to produce "artificial" teas, according to their relative levels in white and green teas, the complete tea exhibited higher antimutagenic potency compared with the corresponding artificial tea. The results suggest that the greater inhibitory potency of white versus green tea in the Salmonella assay might be related to the relative levels of the nine major constituents, perhaps acting synergistically with other (minor) constituents, to inhibit mutagen activation as well as "scavenging" the reactive intermediate(s).

Potent antimutagenic activity of white tea in comparison with green tea in the Salmonella assay

Chlorophyllin is known to inhibit the mutagenicity of a variety of compounds. Using highly purified samples of chlorophyllin and its family compounds, we studied the mechanism of the inhibition. Since mutagens with polycyclic planar structures are particularly strongly inhibited, it seemed likely that the inhibition arises by trapping of the mutagens by chlorophyllin through complex formation at the planar surfaces of these molecules. To explore this possibility, we prepared a Sepharose bearing covalently linked chlorophyllin as ligand, and the adsorption of mutagens to this Sepharose was measured. Three different chlorophyllin derivatives were used, i.e., copper-chlorin, iron-chlorin and chlorin, to investigate the role of metal in the center of the chlorophyllin chromophore. Adsorption of 37 different compounds, mostly mutagens, in 0.02 M Tris-HCl buffer at pH 8.0 to these chlorophyllin-Sepharose preparations was studied in a quantitative manner. The results showed that most of the compounds having three or more fused rings were strongly adsorbed with apparent dissociation constants of 10(-5)-10(-6) M, whereas those having two fused rings or one ring were only poorly adsorbed. Since the three Sepharose adsorbents gave similar adsorption profiles, it appeared that the central metal in the chlorophyllin molecule does not play a crucial role in the adsorption. We also measured the inhibitory effect of copper-chlorin against the mutagenicity of some of these compounds using the Salmonella assay. The results showed that those mutagens that were strongly adsorbable to copper-chlorin-Sepharose were subject to efficient inhibition by copper-chlorin, whereas many of those only poorly adsorbed were inhibited only weakly. We concluded that trapping by complex formation plays a role in the antimutagenic actions of chlorophyllin against many mutagens, particularly notable being the actions against ICR-170, quinacrine, aflatoxin B1, Trp-P-1 and Trp-P-2. An unusual behavior of Trp-P-2 in the adsorption process, i.e., a very tight complex formation at an extremely low Trp-P-2 concentration, was found; the implication of this phenomenon in relation to the real environmental setting is discussed.

Binding of polycyclic planar mutagens to chlorophyllin resulting in inhibition of the mutagenic activity

Inhibitory activity of chlorophyllin on the genotoxicity of carcinogens in Drosophila.

Early work from our laboratory has shown that the mutagenicity of heterocyclic amines in Salmonella can be inhibited by hemin and chlorophyllins. We have speculated that the inhibition is a result of complex formation between heterocyclic amines and the pigments, and the speculation has been given a line of experimental evidence. We have now found that ferric-chlorophyllin (Fe-chlorophyllin) can modify the mutagenicity of 3-hydroxyamino-1-methyl-5 H -pyrido[4,3- b ]indole (Trp-P-2(NHOH)), a metabolically activated form of 3-amino-1-methyl-5 H -pyrido[4,3- b ]indole (Trp-P-2). The mutagenicity of Trp-P-2(NHOH)) in Salmonella typhimurium TA 98 (without S9) was strongly inhibited by an addition of an equimolar Fe-chlorophyllin in the pre-incubation mixture. Fe-chlorophyllin also inhibited the mutagenicity of 2-hydroxyamino-6-methyldipyrido[1,2- a :3′,2′- d ] imidazole (Glu-P-1(NHOH)). A rapid change in the UV spectrum of a mixture of Trp-P-2(NHOH) and Fe-chlorophyllin was observed. Analysis by high performance liquid chromatography showed that Trp-P-2(NHOH) was converted into 3-nitroso-1-methyl-5 H -pyrido[4,3- b ]indole (Trp-P-2(NO)), the mutagenic potency of which is a quarter of that of Trp-P-2(NHOH). Furthermore, the mutagenicity of Trp-P-2(NO), in turn, was inhibited by Fe-chlorophyllin. We conclude that the suppression of the mutagenicity of Trp-P-2(NHOH) is ascribable to the oxidative function of Fe-chlorophyllin, coupled with its ability to form complex formation with the planar surface of the heterocyclic amine molecules.

Iron-chlorophyllin-mediated conversion of 3-hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2(NHOH)) into its nitroso derivative

Antimutagenic and anticarcinogenic activity of chlorophyllin, which is a water-soluble form of chlorophyll, has been reported by many investigators. Chlorophylls, in contrast, have been little studied for this potency. As epidemiological studies suggest that yellow-green vegetables may decrease the risk of human cancers, it is important to explore the antigenotoxic properties of natural chlorophylls. We report here that chlrophylls from spinach and Chlorella can inhibit the mutagenicity of 4-nitroquinoline 1-oxide and 3-amino-1-methyl-5H-pyrido[4,3-b] indole (Trp-P-2) in Drosophila. The chlorophylls also inhibited mutagenesis in Salmonella typhimurium TA98 inducible by Trp-P-2 (NHOH), a direct-acting mutagen. The mechanisms of these inhibitions are discussed.

Hiromi Nakano

Papers

Binding of polycyclic planar mutagens to chlorophyllin resulting in inhibition of the mutagenic activity

Inhibitory activity of chlorophyllin on the genotoxicity of carcinogens in Drosophila.

Iron-chlorophyllin-mediated conversion of 3-hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2(NHOH)) into its nitroso derivative

Inhibitory Activity of Natural Chlorophylls on the Mutagenicity of 4-Nitroquinoline 1-Oxide and 3-Amino-1-Methyl-5H-Pyrido[4,3-b]indole in Drosophila