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M T Huang

Publications and source records attributed to M T Huang.

At least 127 records · Page 7Linked to original sources
PubMed1986

Inhibitory effect of 3-hydroxybenzo(a)pyrene on the mutagenicity and tumorigenicity of (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene.

The 12 isomeric phenols of benzo(a)pyrene were tested for their ability to inhibit the mutagenic activity of (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene [B(a)P 7,8-diol-9,10-epoxide-2], an ultimate mutagenic and carcinogenic metabolite of benzo(a)pyrene. 3-Hydroxybenzo(a)pyrene [3-HO-B(a)P], a major metabolite of benzo(a)pyrene, was the most potent antagonist tested. Approximately 3 nmol of 3-HO-B(a)P, 14 nmol of 10-HO-B(a)P, and 5-8 nmol of 1-, 2-, 4-, 5-, 6-, 7-, 8-, 9-, 11-, and 12-HO-B(a)P inhibited the mutagenic activity of 0.05 nmol of B(a)P 7,8-diol-9,10-epoxide-2 by 50% in Salmonella typhimurium strain TA 100. The importance of the phenolic group for antimutagenic activity was indicated by the lack of antimutagenic activity of benzo(a)pyrene itself. 3-HO-B(a)P also inhibited the mutagenic activity resulting from the metabolic activation of benzo(a)pyrene and (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene by rat liver microsomes. This inhibition may have resulted from an effect of 3-HO-B(a)P on the metabolic activation of these carcinogens and/or from a direct effect on the action of B(a)P 7,8-diol-9,10-epoxide-2. In a mammalian cell culture system utilizing Chinese hamster V79 cells, 3-HO-B(a)P (8 microM) inhibited the mutagenicity of B(a)P 7,8-diol-9,10-epoxide-2 (0.2 microM) by 50%. Although 3-HO-B(a)P was a potent inhibitor of the mutagenic activity of bay-region diol epoxides of benzo(a)pyrene, dibenzo(a,h)pyrene, and dibenzo(a,i)pyrene in S. typhimurium strain TA 100, higher concentrations of 3-HO-B(a)P were needed to inhibit the mutagenicity of the chemically less reactive benzo(a)pyrene 4,5-oxide and the bay-region diol epoxides of benz(a)anthracene, chrysene, and benzo(c)phenanthrene. Both 3-HO-B(a)P and 10-HO-B(a)P accelerated the disappearance of B(a)P 7,8-diol-9,10-epoxide-2 from 1:9 dioxane-water solutions at pH 7 and 25 degrees C. 3-HO-B(a)P, the most effective antimutagen of the B(a)P phenols tested, was much more reactive with the diol epoxide than 10-HO-B(a)P, the least effective antimutagen. The rate constant for the reaction of 3-HO-B(a)P with the diol epoxide exhibited a nonlinear (greater than first-order) dependence on the concentration of the phenol. Evidence was obtained for covalent adduct formation between the diol epoxide and each of the two phenols.(ABSTRACT TRUNCATED AT 400 WORDS)

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1986

Effects of flavonoids on the metabolism of xenobiotics.

Flavonoids represent a large class of naturally occurring plant constituents that are consumed in substantial amounts by experimental animals and by human beings. The ability of flavonoids to activate or inhibit the principal enzyme system involved in the metabolism of lipophilic xenobiotics, including drugs, carcinogens, insecticides and other environmental pollutants, or to induce the synthesis of this enzyme system may have significant pharmacological and toxicological importance. The significant body of literature which illustrates that flavonoids can modulate the tumorigenic activity of polycyclic hydrocarbons and other chemical carcinogens has been reviewed recently (Slaga, Di Giovanni 1984; Wiebel 1980), but further elucidation of mechanisms of action are needed. Possible effects of flavonoids on the metabolism of lipophilic normal body constituents such as steroids and bile acids should be considered, and additional research is needed to determine the extent to which dietary flavonoids can influence the in vivo metabolism of xenobiotics.

Animals↗
PubMed1985

Stimulatory effect of 1 alpha, 25-dihydroxyvitamin D3 on the formation of skin tumors in mice treated chronically with 7,12-dimethylbenz[a]anthracene.

The effect of 1 alpha, 25-dihydroxyvitamin D3 (1 alpha, 25-(OH)2D3) and its 24,24-difluoro analog on the formation of skin tumors in mice was evaluated in a complete carcinogenesis model using 7,12-dimethylbenz[a]anthracene (DMBA) as the carcinogen. Twice weekly topical application of 0.25-0.50 nmol of 1 alpha, 25-(OH)2D3 or 0.05-0.10 nmol of the difluoro analog of 1 alpha, 25-(OH)2D3 1 hour prior to treatment with 50 nmol DMBA stimulated tumor formation several fold compared to animals receiving DMBA alone. Topical application of 0.50 nmol of 1 alpha, 25-(OH)2D3 24 hours after treatment with DMBA, or half of this dose of the vitamin D3 metabolite, applied 1 hour before and 24 hours after treatment with DMBA, also stimulated tumor formation several fold. These results are in marked contrast to the potent inhibitory effect of 1 alpha, 25-(OH)2D3 and its difluoro analog on the formation of skin tumors in mice promoted by 12-O-tetradecanoylphorbol-13-acetate.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1985

Inhibition of the mutagenicity of bay-region diol-epoxides of polycyclic aromatic hydrocarbons by tannic acid, hydroxylated anthraquinones and hydroxylated cinnamic acid derivatives.

Tannic acid and several hydroxylated anthraquinone and cinnamic acid derivatives inhibited the mutagenic activity of (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo [a]pyrene (B[a]P 7,8-diol-9,10-epoxide-2), an ultimate mutagenic and carcinogenic metabolite of benzo [a]pyrene. The mutagenic activity of 0.05 nmol of B[a]P 7,8-diol-9,10-epoxide-2 towards strain TA 100 of Salmonella typhimurium was inhibited 50% by incubation of the bacteria and the diol-epoxide with tannic acid (0.5 nmol), anthraflavic acid (7 nmol), rufigallol (7 nmol), quinalizarin (10 nmol), alizarin (30 nmol), purpurin (60 nmol), and danthron (88 nmol). Dose-dependent, but weaker antimutagenic activity was observed for quinizarin, and a number of hydroxylated cinamic acid derivatives. Gallic acid and m-digallic acid, major components of tannic acid, possessed less than 1% of the anti-mutagenic activity of tannic acid, although m-digallic acid was over 3 times more active than gallic acid. The anti-mutagenic activity of tannic acid was a result of its interaction with B[a]P 7,8-diol-9,10-epoxide-2 since the rate of disappearance of the diol-epoxide from cell-free solutions in 1:9dioxane:water was markedly stimulated by the polyphenol. Tannic acid was a highly potent inhibitor of the mutagenic activity of the bay-region diol-epoxides of benzo[a]pyrene, dibenzo[a,h]pyrene and dibenzo[a,i]pyrene, but higher concentrations of tannic acid were needed to inhibit the mutagenicity of the chemically less reactive benzo[a]-pyrene 4,5-oxide and the bay-region diol-epoxides of benz[a]-anthracene, chrysene and benz[c]phenanthrene.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1985

Effect of ellagic acid and hydroxylated flavonoids on the tumorigenicity of benzo[a]pyrene and (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene on mouse skin and in the newborn mouse.

Ellagic acid, quercetin and robinetin were tested for their ability to antagonize the tumor-initiating activity of benzo[a]pyrene (B[a]P) and (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]P 7,8-diol-9,10-epoxide-2), the ultimate carcinogenic metabolite of benzo[a]-pyrene. Ellagic acid, robinetin or quercetin (2500 nmol) had no tumor-initiating activity on mouse skin, but the topical application of 2500 nmol of ellagic acid 5 min before a tumor-initiating dose of 200 nmol of B[a]P 7,8-diol-9,10-epoxide-2 caused a 59-66% inhibition in the number of skin tumors per mouse that were observed after 15-20 weeks of promotion with 12-O-tetradecanoylphorbol-13-acetate. Similar treatment with 2500 nmol of robinetin or quercetin caused a statistically insignificant 16-24% inhibition in the tumor-initiating activity of 200 nmol of B[a]P 7,8-diol-9,10-epoxide-2 applied 5 min later. Treatment of mice with 2500 nmol of ellagic acid 5 min before the application of 50 nmol of B[a]P inhibited the mean number of skin tumors per mouse by 28-33% after 15-20 weeks of promotion, but these decreases were not statistically significant. Robinetin and quercetin had little or no effect on the tumor-initiating activity of B[a]P on mouse skin. Treatment of preweanling mice with 1/7, 2/7 and 4/7 of the total dose of ellagic acid (300 nmol), robinetin (1400 nmol), myricetin (1400 nmol) or quercetin (1400 nmol) i.p. on their first, eighth and fifteenth day of life, respectively, did not cause the formation of tumors in animals that were killed 9-11 months later. Similar treatment of preweanling mice with the above doses of the phenolic compounds 10 min before the i.p. injection of a total dose of 30 nmol of B[a]P 7,8-diol-9,10-epoxide-2 during the animal's first 15 days of life caused a 44-75% inhibition in the number of diol-epoxide-induced pulmonary tumors per mouse. Similar treatment with these plant phenols had little or no effect on B[a]P-induced pulmonary tumors.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1985

Metabolic fluxes between [14C]2-deoxy-D-glucose and [14C]2-deoxy-D-glucose-6-phosphate in brain in vivo.

The rates of the phosphorylation and dephosphorylation of 2-deoxyglucose were measured in rat brain in vivo using tracer kinetic techniques. The rate constant for each reaction was estimated from two separate experiments with different protocols for tracer administration. Tracer amounts of [1-14C]2-deoxyglucose (1 microCi) were injected through the internal carotid artery (intraarterial experiment), or through the atrium (intravenous experiment). Brains were sampled by freeze-blowing at various times after the injection. In the intraarterial experiment, the rate constant for the forward reaction from 2-deoxyglucose to 2-deoxyglucose phosphate was calculated by dividing the initial rate of 2-deoxyglucose phosphate production by the 2-deoxyglucose content in brain. The rate constant for the reverse reaction from 2-deoxyglucose phosphate to 2-deoxyglucose was calculated from the decay constant of 2-deoxyglucose phosphate. The rate constants estimated were 10.1 +/- 1.4%/min (SD) and 3.00 +/- 0.01%/min (SD), respectively, for the forward and reverse reactions. In the intravenous experiment, rate constants for both reactions were estimated by compartmental analysis. By fitting data to program SAAM-27, the rate constants for the forward and reverse reactions were estimated as 11.4 +/- 0.4%/min (SD) and 5.1 +/- 0.4%/min (SD), respectively. The rate constants determined were compared to those for the reactions between glucose and glucose-6-phosphate, estimated previously from labeled glucoses. It is concluded that the rate of glucose utilization measured by the 2-deoxyglucose method reflects the rate of the hexokinase reaction and not the rate of glucose utilization or brain energy utilization.

Animals↗
PubMed1984

In vitro and in vivo activation of oxidative drug metabolism by flavonoids.

Several naturally occurring and synthetic flavonoids were studied for their effects on the metabolism of zoxazolamine to 6-hydroxyzoxazolamine. Flavone, nobiletin, tangeretin and 7,8-benzoflavone (50-250 microM) stimulated the metabolism of zoxazolamine by liver microsomes obtained from 5-day-old rats. Evidence was obtained indicating that flavone changed the apparent Km and Vmax values for zoxazolamine hydroxylation. The i.p. administration of 5 mumol of flavone, nobiletin, tangeretin or 7,8-benzoflavone concurrently with 740 nmol of zoxazolamine immediately stimulated the total body metabolism of zoxazolamine to 6-hydroxyzoxazolamine. The magnitude of the flavone-mediated increases in zoxazolamine hydroxylation in vivo was dependent on the dose of flavone and the dose of zoxazolamine administered. The i.p. administration of 5 mumol of flavone caused a 3- to 5-fold stimulation in the in vivo metabolism of 740 to 3000 nmol of zoxazolamine, but flavone had little or no stimulatory effect when 74 nmol of zoxazolamine were administered. Flavone stimulated zoxazolamine metabolism both in vitro and in vivo when control or phenobarbital-treated rats were used, but flavone inhibited the in vitro and in vivo hydroxylation of zoxazolamine when rats induced with 5,6-benzoflavone were studied. Although flavone activated zoxazolamine metabolism in vivo in neonatal rats, flavone did not activate the in vivo metabolism of benzo(a)pyrene. The in vitro addition of the hydroxylated flavonoids apigenin, chrysin, fisetin, morin and quercetin inhibited the hydroxylation of zoxazolamine by liver microsomes from neonatal rats, but studies with quercetin and apigenin indicated that these flavonoids had no effect on the in vivo metabolism of zoxazolamine.

Animals↗
PubMed1983

1 alpha, 25-Dihydroxyvitamin D3 inhibits phorbol ester-dependent chemical carcinogenesis in mouse skin.

The effect of topical application of 1 alpha, 25-dihydroxyvitamin D3 (1 alpha, 25-(OH)2D3) on the promotional phase of skin tumor formation in mice was evaluated using 7,12-dimethylbenz [a] anthracene as the tumor initiator and 12-0-tetradecanoylphorbol-13-acetate (TPA) as the tumor promoter. Fifteen weeks of twice weekly topical application of 1 alpha, 25-(OH)2D3 1 hour prior to topical treatment with 16 nmol of TPA inhibited tumor formation in a dose-dependent manner. Doses of 0.25-0.50 nmol of the vitamin D3 metabolite inhibited tumor formation approximately 50% and had no significant effect on the survival or weight gain of the mice. These results indicate that in addition to maintaining calcium homeostasis and affecting the growth and differentiation of certain neoplastic cells, 1 alpha, 25-(OH)2D3 can also suppress the formation of chemically induced tumors.

Administration, Topical↗
PubMed1983

Inhibition of the mutagenicity of bay-region diol-epoxides of polycyclic aromatic hydrocarbons by phenolic plant flavonoids.

Myricetin, robinetin and luteolin inhibited the mutagenic activity resulting from the metabolic activation of benzo[a]-pyrene and (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]-pyrene by rat liver microsomes. These naturally occurring plant flavonoids and seventeen additional flavonoids and related derivatives with phenolic hydroxyl groups inhibited the mutagenic activity of (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene (B[a]P 7,8-diol-9,10-epoxide-2), which is an ultimate mutagenic and carcinogenic metabolite of benzo[a]pyrene. Several flavonoids without phenolic hydroxyl groups or with methylated phenolic hydroxyl groups were inactive. The mutagenic activity of 0.05 nmol of BP 7,8-diol-9,10-epoxide-2 towards strain TA 100 of S. typhimurium was inhibited 50% by incubation of the bacteria and the diol-epoxide with myricetin (2 nmol), robinetin (2.5 nmol), luteolin (5 nmol), quercetin (5 nmol), 7-methoxyquercetin (5 nmol), rutin (5 nmol), quercetin (5 nmol), delphinidin chloride (5 nmol), morin (10 nmol), myricitrin (10 nmol), kaempferol (10 nmol), diosmetin (10 nmol), fisetin (10 nmol), or apigenin (10 nmol). Considerably less antimutagenic activity was observed for dihydroquercetin, naringenin, robinin, D-catechin, genistein, kaempferide and chrysin. Pentamethoxyquercetin, tangeretin, nobiletin, 7,8-benzoflavone, 5,6-benzoflavone, and flavone, which lack free phenolic groups, were inactive. The antimutagenic activity of hydroxylated flavonoids results from their direct interaction with B[a]P 7,8-diol-9,10-epoxide-2 since the rate of disappearance of the diol-epoxide from cell-free solutions in 1:9 dioxane:water was markedly stimulated by myricetin, robinetin and quercetin. Myricetin was a highly potent inhibitor of the mutagenic activity of bay-region diol-epoxides of benzo[a]pyrene, dibenzo[a,h]pyrene and dibenzo[a,i]pyrene, but higher concentrations of myricetin were needed to inhibit the mutagenicity of the chemically less reactive benzo[a]pyrene 4,5-oxide and bay region diol-epoxides of benz[a]anthracene, chrysene and benzo[c]phenanthrene.

Animals↗
PubMed1983

Betamethasone-mediated activation of biphenyl 2-hydroxylation in rat liver microsomes. Studies on possible mechanisms.

The addition of the steroid betamethasone to intact or detergent-solubilized rat liver microsomes caused a concentration-dependent increase in the rate of biphenyl 2-hydroxylation. Betamethasone (100 microM) increased the apparent Vmax for 2-hydroxybiphenyl formation 2- to 4-fold but had no effect on the apparent Km when either the biphenyl or NADPH concentration was varied. Betamethasone had little or no effect on the apparent Vmax or apparent Km of the 3- and 4-hydroxylations of biphenyl. The steroid did not enhance biphenyl 2-hydroxylation through a peroxidative mechanism. Betamethasone had little or no effect on the rate of the NADPH-dependent reduction of cytochrome c or total microsomal cytochrome P-450. The addition of purified NADPH-cytochrome P-450 reductase to cholate-solubilized liver microsomes increased the rate of hydroxylation of biphenyl in positions 2 and 4. Betamethasone (100 microM) decreased the apparent Km for purified cytochrome P-450 reductase by 48% and increased the apparent Vmax of 2-hydroxybiphenyl formation by 2-fold when the concentration of cytochrome P-450 reductase was varied. The steroid did not alter the Km or Vmax values for the 4-hydroxylation of biphenyl. The data suggest that betamethasone enhances the interaction between the reductase and the form(s) of cytochrome P-450 responsible for the 2-hydroxylation of biphenyl.

Animals↗
PubMed1982

Inhibition of the mutagenicity of bay-region diol epoxides of polycyclic aromatic hydrocarbons by naturally occurring plant phenols: exceptional activity of ellagic acid.

Ferulic, caffeic, chlorogenic, and ellagic acids, four naturally occurring plant phenols, inhibit the mutagenicity and cytotoxicity of (+/-)-7beta,8alpha-dihydroxy-9alpha, 10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]P 7,8-diol-9,10-epoxide-2), the only known ultimate carcinogenic metabolite of benzo[a]pyrene. The mutagenicity of 0.05 nmol of B[a]P 7,8-diol-9,10-epoxide-2 in strain TA100 of Salmonella typhimurium is inhibited 50% by incubation of the bacteria and the diol epoxide with 150 nmol of ferulic acid, 75 nmol of caffeic acid, 50 nmol of chlorogenic acid or, most strikingly, 1 nmol of ellagic acid in the 0.5-ml incubation mixture. A 3-nmol dose of ellagic acid inhibits mutation induction by 90%. Ellagic acid is also a potent antagonist of B[a]P 7,8-diol-9,10-epoxide-2 in Chinese hamster V79 cells. Mutations to 8-azaguanine resistance induced by 0.2 muM diol epoxide are reduced by 50% when tissue culture media also contains 2 muM ellagic acid. Similar to results obtained with the bacteria, ferulic, caffeic, and chlorogenic acids are approximately two orders of magnitude less active than ellagic acid in the mammalian cell assay. The antimutagenic effects of the plant phenols result from their direct interaction with B[a]P 7,8-diol-9,10-epoxide-2, because a concentration-dependent increase in the rate of diol epoxide disappearance in cell-free solutions of 1:9 dioxane/water, pH 7.0, is observed with all four phenols. In parallel with the mutagenicity studies, ellagic acid is 80-300 times more effective than the other phenols in accelerating the disappearance of B[a]P 7,8-diol-9,10-epoxide-2. Ellagic acid at 10 muM increases the disappearance of B[a]P 7,8-diol-9,10-epoxide-2 by approximately 20-fold relative to the spontaneous and hydronium ion-catalyzed hydrolysis of the diol epoxide at pH 7.0. Ellagic acid is a highly potent inhibitor of the mutagenic activity of bay-region diol epoxides of benzo[a]pyrene, dibenzo[a,h]pyrene, and dibenzo[a,i]pyrene, but higher concentrations of ellagic acid are needed to inhibit the mutagenic activity of the chemically less reactive bay-region diol epoxides of benz[a]anthracene, chrysene, and benzo[c]phenanthrene. These studies demonstrate that ellagic acid is a potent antagonist of the adverse biological effects of the ultimate carcinogenic metabolites of several polycyclic aromatic hydrocarbons and suggest that this naturally occurring plant phenol, normally ingested by humans, may inhibit the carcinogenicity of polycyclic aromatic hydrocarbons.

Animals↗
PubMed1982

Disappearance of exercise-induced ST-segment depression associated with transient left anterior hemiblock.

To our knowledge, this is the first case reported of total disappearance of exercise-induced ST-segment depression in the presence of transient left anterior hemiblock at peak exercise. An unusual paradoxic increase in T-wave amplitude was also noticed. The significant ST-segment displacement reappeared when the transient left anterior hemiblock disappeared during the recovery phase. Based on current review, the presence of transient left anterior hemiblock during exercise seems to correlate well with the proximal left anterior descending coronary artery disease. Therefore, the presence of transient left anterior hemiblock during exercise with either normalization of exercise-induced ST-segment depression or paradoxic increase in T-wavse amplitude at peak level may be a useful end-point to stop the test for patients who do not reach 2 mm ST-segment depression or who remain asymptomatic.

Adult↗
PubMed1981

Specificity in the activation and inhibition by flavonoids of benzo[a]pyrene hydroxylation by cytochrome P-450 isozymes from rabbit liver microsomes.

The effect of flavone and 7,8-benzoflavone on the metabolism of benzo[a]pyrene to fluorescent phenols by five cytochrome P-450 isozymes obtained from rabbit liver microsomes was determined. Benzo[a]pyrene metabolism was stimulated more than 5-fold by the addition of 600 microM flavone to a reconstituted monooxygenase system consisting of NADPH, cytochrome P-450 reductase, dilauroylphosphatidylcholine, and cytochrome P-450LM3c or cytochrome P-450LM4. In contrast, an inhibitory effect of flavone on benzo[a]pyrene metabolism was observed when cytochrome P-450LM2, cytochrome P-450LM3b, or cytochrome P-450LM6 was used in the reconstituted system. 7,8-Benzoflavone (50-100 microM) stimulated benzo[a]pyrene metabolism by the reconstituted monooxygenase system about 10-fold when cytochrome P-450LM3c was used, but benzo[a]pyrene hydroxylation was strongly inhibited when 7,8-benzoflavone was added to the cytochrome P-450LM6-dependent system. Smaller effects of 7,8-benzoflavone were observed on the metabolism of benzo[a]pyrene by the cytochrome P-450LM2-, cytochrome P-450LM3b-, and cytochrome P-450LM4-dependent monooxygenase systems. These results demonstrate that the activating and inhibiting effects of flavone and 7,8-benzoflavone on benzo[a]pyrene metabolism depend on the type of cytochrome P-450 used in the reconstituted monooxygenase system.

Animals↗