Inhibition of microsomal activation of aflatoxin B1 by 3-dehydroretinol and 3-dehydroretinyl palmitate.

Two vitamin A2 compounds (3-dehydroretinol and 3-dehydroretinyl palmitate) which are predominantly present in fresh water fish have been found to be very effective in inhibiting the microsome catalysed formation of DNA adduct by the carcinogen aflatoxin B1. The inhibition appears to be due to modulation of microsomal enzymes which activate the carcinogen. Such inhibition may suggest a potential chemopreventive role of these compounds against carcinogenesis induced by aflatoxin B1.

Action of curcumin on the cytochrome P450-system catalyzing the activation of aflatoxin B1.

Curcumin, in a dose-dependent manner, inhibited the formation of covalent adduct between aflatoxin B1 and DNA, as catalyzed by microsomes or a reconstituted microsomal monooxygenase system. Its effect on the cytochrome P450-system was investigated in the latter system. The inhibition (50%) of aflatoxin B1-DNA adduct formation by curcumin in this system could be reversed by increasing the amount of cytochrome P450 but not by that of NADPH-cytochrome P450 reductase.

In vivo effect of dietary factors on the molecular action of aflatoxin B1: role of non-nutrient phenolic compounds on the catalytic activity of liver fractions.

Young adult rats were kept on a synthetic diet containing various food associated phenolic compounds each at 0.5% level. The ability of liver microsomes to catalyze reactions of aflatoxin B1 leading to its activation and DNA adduct formation was measured after an experimental feeding period of 3 weeks.

Modulatory effects of essential oils from spices on the formation of DNA adduct by aflatoxin B1 in vitro.

Essential oils from common spices such as nutmeg, ginger, cardamom, celery, xanthoxylum, black pepper, cumin, and coriander were tested for their ability to suppress the formation of DNA adducts by aflatoxin B1 in vitro in a microsomal enzyme-mediated reaction. All oils were found to inhibit adduct formation very significantly and in a dose-dependent manner. The adduct formation appeared to be modulated through the action on microsomal enzymes, because an effective inhibition on the formation of activated metabolite was observed with each oil.

In vivo effect of dietary factors on the molecular action of aflatoxin B1: role of riboflavin on the catalytic activity of liver fractions.

Weanling rats were kept on a synthetic riboflavin-free diet for 4 weeks, and subsequently on the same diet but supplemented with riboflavin for 2 weeks. The ability of liver microsomes to catalyze reactions of aflatoxin B1 (AFB1) leading to its activation and DNA adduct formation was measured after each period of experimental feeding. A decrease in both activities was evident during riboflavin deficiency, and this could be restored after normal supply of the vitamin.

In vivo effect of dietary factors on the molecular action of aflatoxin B1: role of copper on the catalytic activity of liver microsome.

Wealing rats were kept on a synthetic copper-free diet for 9-13 weeks and subsequently on the same diet but supplemented with copper at different levels for 2 weeks. The ability of liver microsomes to catalyze reactions of aflatoxin B1 leading to its activation and DNA adduct formation was measured after each period of experimental feeding. An increased molecular reactivity of aflatoxin B1 was evident during deficiency such that the degree of its conversion to its reactive metabolite and subsequent DNA adduct formation was higher with microsomes from copper deficient rats as compared to rats maintained on a normal supply of copper.

Modulation of flavocoenzyme levels in rat tissues by N-nitrosodiethylamine.

The hepatocarcinogen N-nitrosodiethylamine (NDEA) was administered continuously in drinking water (200 mg/l) to male Wistar rats, and at intervals tissues were examined for flavocoenzyme levels. Flavin adenine dinucleotide (FAD) and non-FAD riboflavin were determined fluorimetrically. Results revealed significant depletion in hepatic levels of these compounds at the end of 60 days, a period of exposure considered adequate for the development of hepatoma.

In vivo effect of dietary factors on the molecular action of aflatoxin B1: role of vitamin A on the catalytic activity of liver fractions.

Weanling rats were kept on a synthetic vitamin A free diet for 9 weeks, and subsequently on the same diet but with oral supplementation of vitamin A palmitate at different doses for 2-3 weeks. The ability of liver microsomes to catalyze reactions of aflatoxin B1 (AFB1) leading to its activation and DNA adduct formation was measured after each period of experimental feeding. An increased molecular reactivity of AFB1 was evident during vitamin A deficiency such that the degree of its conversion to its reactive metabolite and subsequent DNA adduct formation was higher with microsomes from vitamin A-deficient rats as compared to rats maintained on normal supply of vitamin A.

Action of vitamin A on DNA adduct formation by aflatoxin B1 in a microsome catalyzed reaction.

The effect of vitamin A and some derivatives has been studied on the formation of DNA adduct by aflatoxin B1 (AFB1) in an in vitro reaction catalyzed by rat liver microsomes. Retinol, retinal, all trans retinoic acid and two retinyl esters were found to inhibit the adduct formation in a dose-dependent manner. The inhibition by retinol showed that it was prompt and could be reversed by increasing microsome concentration.

Modulation by certain factors of metabolic activation of aflatoxin B1 as detected in vitro in a simple fluorimetric assay.

Forty compounds belonging to various chemical groups have been tested for their ability to suppress metabolic activation of aflatoxin B1 (AFB1) mediated by rat liver microsome. Microsomal activation has been carried out in an in vitro system containing Tris-buffer at pH 7.2.

Factors modulating the formation of DNA adduct by aflatoxin B1 in vitro.

Forty-two compounds belonging to various chemical groups have been tested for their ability to suppress formation of aflatoxin B1--DNA adduct mediated by microsome in vitro. While many of these compounds have either marginal or no modulating effect, some have been identified as effective inhibitors. The strong inhibition of DNA adduct formation by retinoids (retinol, retinal, retinoic acid and retinyl acetate), riboflavin, riboflavin 5'-phosphate, flavin adenine dinucleotide, Cu2+, 7,8-benzoflavone, disulfiram, butylated hydroxyanisole, butylated hydroxytoluene and phenothiazine suggests that these agents may have potential anticarcinogenic activity against aflatoxin B1.