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A R Francis

Publications and source records attributed to A R Francis.

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Modifying role of dietary factors on the mutagenicity of aflatoxin B1: in vitro effect of plant flavonoids.

Eighteen flavonoids have been tested for their ability to inhibit the mutagenicity of aflatoxin B1 (AFB1) towards strains TA100 and TA98 of Salmonella typhimurium provided with a rat liver activation system. These flavonoids belong to 5 different groups: flavone, isoflavone, flavanone, flavanol and flavonol, and many individual members are natural products present in edible portions of a variety of food plants. Several flavonoids exhibited significant inhibitory ability in both strains. Flavonols in general are more active in this regard, while flavanones show a strain-specific response. The flavanol group of compounds did not display any activity. Among the most effective flavonoids are kaempferol, morin, fisetin, biochanin A and the glycoside rutin, all of which exhibit a dose-dependent inhibition pattern. Kaempferol and rutin, in particular, show exceptional activity inasmuch as, on a molar basis, only a 10-fold excess dose of each can inhibit the mutagenic activity of AFB1 in strain TA98 by 50%. The action of flavonoids is possibly mediated through interaction with microsomal activating enzymes. Previous evidence from this laboratory about their inhibitory action on DNA-adduct formation and metabolic activation together with the present results suggests that certain flavonoids, notably polyhydroxylated flavonols, may have potential anticarcinogenic activity against AFB1.

Aflatoxin B1↗

Modifying role of dietary factors on the mutagenicity of aflatoxin B1: in vitro effect of sulphur-containing amino acids.

Sulphur-containing amino acids including some derivatives have been tested for their effectiveness in suppressing the mutagenic activity of aflatoxin B1 in Salmonella typhimurium strains provided with a rat liver activation system. Cysteine and N-acetylcysteine have been found to be most effective in the 2 strains tested (TA100 and TA98). Glutathione (oxidised and reduced forms) has shown partial activity, while cystine and methionine are found to be partially effective only in strain TA100. Inhibition of mutagenicity may be due to interaction of these substances with microsomal enzymes resulting in interference with the formation of ultimate mutagenic species.

Aflatoxin B1↗

Modification of the mutagenicity of aflatoxin B1 and N-methyl-N'-nitro-N-nitrosoguanidine by certain phenolic compounds.

Five natural and two synthetic phenolic compounds were tested for their ability to suppress mutagenicity of aflatoxin B1 (AFB1) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in Salmonella typhimurium tester strain TA100. Caffeic acid and eugenol were observed to inhibit mutagenicity of both the carcinogens, while chlorogenic acid was effective in the case of AFB1 alone and ellagic acid and butylated hydroxytoluene were found to be antimutagenic only for MNNG. These differential activities of the phenolic compounds appeared to be due to their different modes of action towards direct and indirect acting carcinogens.

Aflatoxin B1↗

Modulating effect of plant flavonoids on the mutagenicity of N-methyl-N'-nitro-N-nitrosoguanidine.

Tests have been carried out with several plant flavonoids to detect their ability to suppress mutagenesis in Salmonella typhimurium strain TA100 NR induced by the direct-acting carcinogen N-methyl-N'-nitro-N-nitrosoguanidine. Among the most effective flavonoids are the isoflavone, biochanin A, the flavanone glycoside, naringin, and its aglycone, naringenin, and several flavonols, e.g. morin, fisetin, kaempferol, gossypetin and quercetin, including a flavonol glycoside, rutin. In particular, naringin possesses exceptional antimutagenic activity, in as much as, less than half the equimolar amount can reduce the mutagenic potency of this carcinogen by 50%. These flavonoids appear to act either by preventing passage of the carcinogen into bacterial cells or by altering some cellular processes.

Flavonoids↗

Modifying role of dietary factors on the mutagenicity of aflatoxin B1: in vitro effect of trace elements.

Using Salmonella typhimurium strains TA100 and TA98 tests have been carried out to detect the inhibitory activity of various trace elements on mutagenesis induced by aflatoxin B1 (AFB1) in the presence of a rat liver microsomal activation system. Several trace elements have shown significant modulating activity in both the strains, while a few show inhibition only in a particular strain. Among the most effective elements are copper, manganese, zinc and selenium, all of which exhibit an inhibition pattern which is dose-dependent. Copper, in particular, shows exceptional activity, since the molar excess dose of this element required to inhibit AFB1 mutagenicity by 50% has been observed to be very low. The action of trace elements is possibly mediated through interaction with microsomal enzymes, thereby modulating the formation of the reactive metabolite before modification of DNA. These results suggest that certain trace elements notably copper may have potential anticarcinogenic activity against AFB1.

Aflatoxin B1↗

Effect of certain trace elements on the mutagenicity of N-methyl-N'-nitro-N-nitrosoguanidine.

Tests have been carried out to detect inhibitory activity of various trace elements on mutagenesis induced by the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine in Salmonella typhimurium strain TA100. Selenium has been found to be most active in this regard while copper has displayed moderate inhibitory ability. The action of selenium is mediated through an interaction resulting in rapid deactivation of the carcinogen.

Copper↗

Modifying role of vitamins on the mutagenic action of N-methyl-N'-nitro-N-nitrosoguanidine.

Several vitamin compounds have been tested for their ability to suppress the mutagenicity of N-methyl-N'-nitro-N-nitrosoguanidine, a direct acting mutagen/carcinogen, in Salmonella typhimurium strain TA100. Menadione, alpha-tocopherol, retinal and retinol have displayed high inhibitory activity. The antimutagenic activity of menadione, in particular, has been found to be remarkable in as much as less than equimolar amount can reduce the mutagenic potency of the carcinogen by 50%. In vitro data suggest that its action is mediated by accelerating the deactivation of the N-nitroso carcinogen, possibly involving the formation of a quinone radical.

Methylnitronitrosoguanidine↗

Modifying role of dietary factors on the mutagenicity of aflatoxin B1: in vitro effect of vitamins.

19 vitamins including some derivatives have been tested for their ability to suppress mutagenic activity of aflatoxin B1 (AFB1) towards Salmonella typhimurium strain TA100 activated with a rat-liver metabolic activation system. Several vitamins have shown an ability to inhibit the mutagenic potency of AFB1. The values of ID50, i.e. the dose required to inhibit mutagenic activity by 50% calculated from dose-response curves for each vitamin show retinoids, riboflavin, folic acid, menadione, cyanocobalamin, ascorbic acid and pyridoxine to be significantly antimutagenic. Although inhibition by vitamins is apparent over a range of AFB1 concentrations, their effect is more pronounced at lower concentrations of AFB1. When combined data are expressed in terms of specific mutagenicity, riboflavin, retinol and menadione have been found to possess exceptional inhibitory ability in as much as, on a molar basis, only 15-40-fold excess vitamins can inhibit the mutagenic potency of AFB1 by 50%. Their action is possibly mediated through interaction with microsomal activating enzymes. Previous evidence from this laboratory about their inhibitory action on DNA-adduct formation and metabolic activation together with the present results suggest that certain vitamins notably retinoids and riboflavin may have potential anticarcinogenic activity against AFB1.

Aflatoxin B1↗