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PubMed2005

Diallyl disulfide inhibits N-acetyltransferase activity and gene expression in human esophagus epidermoid carcinoma CE 81T/VGH cells.

Individuals can be classified into rapid or slow acetylators based on the N-acetyltransferase (NAT) activity which is believed to affect cancer risk that is related to environmental carcinogen exposure. Diallyl disulfide (DADS) is a naturally occurring organosulfur compound, from garlic (Allium sativum), which exerts anti-neoplasm activity. In this study, we investigated the inhibitory effects of DADS on NAT activity and gene expresseion (NAT mRNA) in human esophagus epidermoid carcinoma CE 81T/VGH cells. NAT activity was measured by the amounts of N-acetylation of 2-aminofluorene (AF) and non-acetylation of AF by high performance liquid chromatography on cells treated with or without DADS. The amounts of NAT enzymes were examined and analyzed by Western blot. NAT gene expression (NAT mRNA) was examined by polymerase chain reaction and cDNA microarray. DADS decreased the amount of N-acetylation of AF in human esophagus epidermoid carcinoma CE 81T/VGH cells in a dose-dependent manner. Western blot analysis indicated that DADS decreased the levels of NAT protein in CE 81T/VGH cells. PCR and cDNA microarray experiments showed that DADS affected NAT1 mRNA expression in CE 81T/VGH cells. DADS affect NAT activity due to the inhibition of gene expression (NAT1 mRNA) and the decreasing of the protein levels of NAT in CE 81T/VGH cells.

Acetylation↗
PubMed2004

Effect of surface tarp on emissions and distribution of drip-applied fumigants.

Soil fumigants are used to control a wide variety of soil-borne pests in high-cash-value crops. Application of soil fumigants through drip irrigation systems is receiving increasing attention as a method to improve the uniformity of fumigant application. Little information is available on the emissions and soil distribution of fumigants following subsurface drip application, or the effect of plastic tarp on fumigant emissions in these systems. In these experiments, the fumigant compounds 1,3-dichloropropene (1,3-D), Vapam (a methyl isothiocyanate (MITC) precursor), and propargyl bromide (PrBr) were applied to soil beds via drip irrigation at 15 cm depth. Beds were tarped with either standard 1-mil high-density polyethylene (HDPE) or a virtually impermeable film (VIF), leaving the furrows bare. Cumulative emissions of 1,3-D, MITC, and PrBr in these tarped bedded systems was very low, amounting to <10% of the applied mass. These experiments were conducted in the winter months, with average air temperatures of 12-15 degrees C. Cumulative emissions of MITC and 1,3-D from a sandy loam field soil were decreased by > or =80% by tarping the bed with VIF rather than HDPE. A large fraction of the 1,3-D and PrBr flux was from the untarped furrows in VIF-tarped plots, indicating that inhibiting volatilization from the furrow will be important in further reducing emissions in these systems. Monitoring the fumigant distribution in soil indicated that tarping the bed with VIF resulted in a more effective containment of fumigant vapors compared to use of a HDPE tarp.

Air Movements↗
PubMed2004

Relaxation filtered hyperfine (REFINE) spectroscopy: a novel tool for studying overlapping biological electron paramagnetic resonance signals applied to mitochondrial complex I.

A simple strategy to separate overlapping electron paramagnetic resonance (EPR) signals in biological systems is presented. Pulsed EPR methods (inversion- and saturation-recovery) allow the determination of the T(1) spin-lattice relaxation times of paramagnetic centers. T(1) may vary by several orders of magnitude depending on the species under investigation. These variations can be employed to study selectively individual species from a spectrum that results from an overlap of two species using an inversion-recovery filtered (IRf) pulsed EPR technique. The feasibility of such an IRf field-swept technique is demonstrated on model compounds (alpha,gamma-bisphenylene-beta-phenylallyl-benzolate, BDPA, and 2,2,6,6-tetramethyl-piperidine-1-oxyl, TEMPO) and a simple strategy for the successful analysis of such mixtures is presented. Complex I is a multisubunit membrane protein of the respiratory chain containing several iron-sulfur (FeS) centers, which are observable with EPR spectroscopy. It is not possible to investigate the functionally important FeS cluster N2 separately because this EPR signal always overlaps with the other FeS signals. This cluster can be studied selectively using the IRf field-swept technique and its EPR spectrum is in excellent agreement with previous cw-EPR data from the literature. In addition, the possibility to separate the hyperfine spectra of two spectrally overlapping paramagnetic species is demonstrated by applying this relaxation filter together with hyperfine spectroscopy (REFINE). For the first time, the application of this filter to a three-pulse electron spin-echo envelope modulation (ESEEM) pulse sequence is demonstrated to selectively observe hyperfine spectra on a system containing two paramagnetic species. Finally, REFINE is used to assign the observed nitrogen modulation in complex I to an individual iron-sulfur cluster.

Allyl Compounds↗
PubMed2006

Reducing 1,3-dichloropropene emissions from soil columns amended with thiourea.

Soil fumigants are becoming an important source of volatile organic compounds (VOCs) in air, especially in some agricultural areas. In this study, we used thiourea to construct a reactive surface barrier (RSB) at the soil surface for reducing 1,3-dichloropropene (1,3-D) volatilization. The agrochemical thiourea could rapidly transform volatile 1,3-D to nonvolatile products via an SN2 nucleophilic substitution reaction. A catalytic mechanism in thiourea-amended soil facilitated the conversion process. A packed soil column system was employed to investigate the emissions and distribution of 1,3-D and optimize the original fumigant emission-reduction strategy. Volatilization of 1,3-D from the soil surface was significantly reduced in columns amended with a thiourea RSB compared with that of bare soil. Volatilization flux and cumulative emissions decreased with increasing thiourea application rate and increasing fumigation depth in packed soil columns. Surface amendment with the RSB did not affect the subsurface distribution of 1,3-D in the soil profile. Combined application of a thiourea RSB and plastic tarps had a synergetic effect in emission control and could eliminate the relatively high fumigant flux that occurs upon tarp disruption. Therefore, this reduced-risk practice was very effective in reducing atmospheric emissions of VOCs from soil treatment with halogenated fumigants.

Allyl Compounds↗
PubMed2004

Experimental study on the prevention and treatment of murine cytomegalovirus hepatitis by using allitridin.

Allitridin (diallyl trisulfide), a main effective compound of Allium sativum (garlic), was previously shown to inhibit the expression of immediate-early antigens and viral proliferation of human cytomegalovirus (HCMV) in vitro. Here we have examined the prophylactic and therapeutic efficacy of allitridin in a non-lethal murine cytomegalovirus (MCMV) hepatitis in methylprednisolone-immunosuppressed BALB/c mice. Allitridin was administered at 25mg/kg per day (equal to the mean human dose) and 75 mg/kg per day in two regimens: prophylaxis plus therapy beginning at 2 days before infection and lasting for 18 days, and therapy lasting for 14 days initiated at 2 days after infection. Ganciclovir (GCV)-treated, infected, and non-infected mice served as controls. MCMV DNA load in the liver, plasma alanine aminotransferase (ALT) level and Knodell's histological activity index (HAI) score of liver section were evaluated. We found that MCMV DNA load was significantly decreased in all allitridin- and GCV-treated mice, compared with infected controls. Concomitantly, histopathological lesions in the liver and plasma ALT levels were reduced. Statistically, no significant differences were detected between the combined allitridin prophylaxis plus therapeutic and therapeutic groups regardless of dose and the GCV groups. Our results demonstrate the therapeutic efficacy of allitridin in mouse models with MCMV hepatitis.

Allyl Compounds↗
PubMed2004

Reversal of P-glycoprotein-mediated multidrug resistance by diallyl sulfide in K562 leukemic cells and in mouse liver.

Multidrug resistance (MDR) mediated by the overexpression of drug efflux protein P-glycoprotein (P-gp) is one of the major obstacles to successful cancer chemotherapy. P-gp acts as an energy-dependent drug efflux pump, reducing the intracellular concentration of structurally unrelated drugs. Modulators of P-gp function can restore the sensitivity of multidrug-resistant cells to such drugs. In the present study, we evaluated the P-gp modulatory potential of diallyl sulfide (DAS), a volatile organosulfur compound present in garlic, known to possess many medicinal properties, including antimutagenic and anticarcinogenic activities. For in vitro studies, K562 leukemic cells were made resistant (K562/R) to the cytotoxicity of vinblastine (VBL) by progressive adaptation of the sensitive K562 parental cells to VBL. Cross-resistance of K562/R was found between vincristine (VCR), doxorubicin and other antineoplastic agents. A non-toxic concentration of DAS (8.75 x 10(-3) M) enhanced the cytotoxic effects of VBL and another vinca alkaloid, VCR, time dependently in VBL-resistant human leukemia (K562/R10) cells but had no effect on the parent (K562/S) cells. The results show that DAS decreased the induced levels of P-gp in resistant cells back to the normal levels as analyzed both qualitatively and quantitatively by western blotting and immunocytochemistry. Furthermore, in vivo combination studies showed that DAS effectively inhibited vinca alkaloid-induced P-gp overexpression in mouse hepatocytes. Quantitation of immunostained tissue sections with image analysis showed that the reduction in P-gp levels was up to 73% for VBL- and 65% for VCR-induced drug resistance. The above features thus indicate that DAS can serve as a novel, non-toxic modulator of MDR and can be used as a dietary adjuvant.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1999

Metabolism of diallyl disulfide by human liver microsomal cytochromes P-450 and flavin-containing monooxygenases.

The metabolism of diallyl disulfide (DADS), a garlic sulfur compound, was investigated in human liver microsomes. Diallyl thiosulfinate (allicin) was the only metabolite observed and its formation followed Michaelis-Menten kinetics with a Km = 0.61 +/- 0.2 mM and a Vmax = 18.5 +/- 4.2 nmol/min/mg protein, respectively (mean +/- S.E. M., n = 4). Both flavin-containing monooxygenase and the cytochrome P-450 monooxygenases (CYP) were involved in DADS oxidation, but the contribution of CYP was predominant. The cytochrome P-450 isoforms involved in this metabolism were investigated using selective chemical inhibitors, microsomes from cells expressing recombinant CYP isoenzymes, and studying the correlation of the rate of DADS oxidation with specific monooxygenase activities of human liver microsomes. Diethyldithiocarbamate and tranylcypromine inhibited allicin formation, whereas other specific inhibitors had low or no effect. Most of the different human microsomes from cells expressing CYP were able to catalyze this reaction, but CYP2E1 showed the highest affinity with a substantial activity. Furthermore, allicin formation by human liver microsomes was correlated with p-nitrophenol hydroxylase activity, a marker of CYP2E1, and tolbutamide hydroxylase activity, a marker of CYP2C9. Among these approaches only CYP2E1 was identified in each case, which suggested that DADS is preferentially metabolized to allicin by CYP2E1 in human liver. However the minor participation of other CYP forms and flavin-containing monooxygenases is likely.

Allyl Compounds↗
PubMed2002

Diallyl disulfide increases rat h-ferritin, L-ferritin and transferrin receptor genes in vitro in hepatic cells and in vivo in liver.

Of the oil-soluble organosulfur compounds derived from garlic, diallyl disulfide (DADS) is one of the most abundant. We examined the effect of DADS on gene expression in rat liver. By suppressive subtractive hybridization, we identified the heavy (H)-ferritin gene as a DADS-stimulated gene in the rat liver epithelial (REL) cells. DADS stimulation of H- and L (light)-ferritin mRNA was analyzed in REL cells and in rat liver. Incubation of the REL cells in 10 micro mol/L DADS for 4 h increased H-ferritin 1.9 +/- 0.2-fold, n = 3) and light(L)-ferritin mRNA 1.5 +/- 0.2-fold, n = 3). Stimulation did not occur in the presence of an inhibitor of transcription, actinomycin D. Stimulation of ferritin at the RNA and protein levels was also found in rats administered a DADS-enriched oil solution intragastrically. There was a 3 +/- 1.1-fold increase in H- and 3 +/- 0.14-fold increase for L-ferritin mRNA 24 h after the end of the infusion in the presence of DADS, (n = 3). The expression of the transferrin receptor, an iron transporter, was also enhanced by DADS in rat liver. In conclusion, our data suggest that DADS could modify iron homeostasis through the modulation of ferritin and transferrin receptor gene expression.

Allyl Compounds↗
PubMed2006

Dehalogenation of halogenated fumigants by polysulfide salts.

Halogenated fumigants are among the most heavily used pesticides in agriculture. Because of their high mobility and toxicological characteristics, the contamination of air or groundwater by these compounds has been a great environmental concern. In this study, we investigated dehalogenation of several halogenated fumigants by polysulfides. The reaction of polysulfides and methyl iodide (MeI), 1,3-dichloropropene (1,3-D), and chloropicrin (CP) was very rapid. When the initial fumigant and polysulfide concentrations were both 0.2 mM, the observed 50% disappearance time values (DT50) of MeI, cis-1,3-D, and trans-1,3-D were 27.2, 29.6, and 102 h, respectively. When the initial polysulfide concentration was 1.0 mM, the corresponding DT50 values were only 2.2, 1.6, and 3.8 h. Under similar conditions, the reaction with CP was even more rapid than with the other fumigants. In 0.2 mM polysulfide solution, more than 90% of the spiked CP disappeared in 1 h after the initiation of the reaction. The reaction between fumigants and polysulfides also progressed at enhanced rates when the polysulfide solution was initially purged with nitrogen. Analysis of reaction kinetics and initial products suggests that the reaction is SN2 nucleophilic substitution for MeI and 1,3-D but likely reductive dehalogenation for CP. Given the high reactivity of polysulfide salts toward halogenated fumigants, this reaction may be used as a pollution mitigation strategy, such as for disposal of fumigant wastes, treatment of fumigant-containing wastewater, and cleanup of fumigant residues in environmental media.

Allyl Compounds↗
PubMed1993

MDL 72,974A: a selective MAO-B inhibitor with potential for treatment of Parkinson's disease.

MDL 72,974A [(E)-2-(4-fluorophenethyl)-3-fluoroallylamine, hydrochloride] was designed to be a selective, mechanism-based irreversible inhibitor of monoamine oxidase type B (MAO-B). The compound is a potent, selective MAO-B inhibitor in vitro and in vivo. In vitro studies revealed an IC50 value (MAO-B) of 3.6 nM with 189-fold selectivity compared to MAO-A. In rats, profound inhibition of MAO-B was achieved after a single oral dose with an ED50 of 0.18 mg/kg; a dose 44 times this amount was required to inhibit MAO-A by 50%. Selectivity was maintained following chronic dosing. MDL 72,974A had minimal sympathomimetic effects and did not potentiate the cardiovascular effects of tyramine, even at 50 times the MAO-B inhibiting dose. This inhibitor was equally effective and well-tolerated in man. In human volunteers, potent inhibition of platelet MAO-B activity was observed at submilligram doses (ED50 = 90 micrograms) following a single oral dose. Upon multiple oral doses of 100 micrograms, as much as 80% of MAO-B could be inhibited. In phase II studies, MDL 72,974A is proving to be a useful adjunct to conventional therapy. Patients (250) with Parkinson's disease, treated once daily with either 1 or 4 mg, together with L-Dopa and a decarboxylase inhibitor (MadoparR or SinemetR), saw significant improvements in symptoms compared with those on standard therapy without the inhibitor.

Allyl Compounds↗
PubMed1997

Reducing effects of garlic constituents on DNA adduct formation in human lymphocytes in vitro.

A water extract of raw garlic (RGE) and two organosulfur compounds, diallyl sulfide and S-allylcysteine (SAC), were evaluated for their relative effectiveness in reducing benzo[a]pyrene (BaP)-DNA adduct formation in stimulated human peripheral blood lymphocytes in vitro. In replicate experiments, RGE significantly inhibited BaP-DNA adduct formation at concentrations of 0.001, 0.01, and 0.1 mg/ml. SAC also significantly decreased BaP-DNA adduct formation at concentrations of 0.01 and 0.1 mg/ml. For diallyl sulfide, no significant reduction in BaP-DNA adduct formation was found. BaP-DNA adduct formation was not associated with cell viability or proliferation of peripheral blood lymphocytes after the various treatments. No clear scavenging activity was detected for the garlic constituents. Aryl hydrocarbon hydroxylase activity was not decreased, nor was formation of sulfate and glucuronide conjugates of 3-hydroxy-BaP increased in the presence of RGE and SAC, indicating that increased glutathione S-transferase activity or a more efficient repair of BaP-DNA adducts may explain the observed effects. In addition, reactive oxygen species-induced 8-oxodeoxyguanosine in DNA was reduced in the presence of SAC. It is concluded that raw garlic and SAC may be useful in the prevention of BaP-associated tumorigenesis and that further evaluation of their preventive potential in humans at risk appears feasible.

Allyl Compounds↗
PubMed1983

Effects of metyrapone on microsomal-dependent Salmonella mutagenesis. Studies with chloroallyl ethers and model compounds.

Metyrapone (2-methyl-1,2-di-3-pyridyl-1-propanone, MTP) is used as an inhibitor of cytochrome P-450 enzymes, particularly those induced by phenobarbital (PB). We examined the effects of MTP on the microsomal dependent mutagenesis of a newly isolated promutagen, 3-(2-chloroethoxy)-1,2-dichloropropene (CP), three S-chloroallyl thiocarbamate herbicides, and four model promutagens aflatoxin B1 (AFB), 2-acetylaminofluorene (2AAF), 2-aminoanthracene (2AA) and benzo[a]pyrene (BP). Salmonella tester strains TA98, TA100 and TA1535 and liver microsomal preparations (S9) from rats induced with PB or Aroclor 1254 (PCB) were employed. For statistical analysis, mutagenesis data were transformed and subjected to two-way analysis of variance. Metyrapone alone was not mutagenic in the absence or presence of S9. In a dose-dependent manner, MTP inhibited mutagenesis of AFB for strains TA98 and TA100 and enhanced mutagenesis of 2AAF, 2AA and BP for these strains. 3-(2-Chloroethoxy)-1, 2-dichloropropene and the herbicides diallate, triallate and sulfallate are all chloroallyl ethers. They are similar in their mutagenesis for Salmonella with respect to strain specificity, mutagenic potency, and requirement for activation by specifically-induced microsomes. Metyrapone inhibited the mutagenesis of CP, triallate and sulfallate for strain TA100 in the presence of either PB- or PCB-induced S9, and had no apparent effect on diallate mutagenesis; the same results were obtained for TA1535 with PCB-induced S9. On this basis, the mutagenic activation of diallate appears to be different from that of the other chloroallyl ethers tested. Our results indicate that MTP can inhibit as well as enhance microsomal dependent mutagenesis for Salmonella. We conclude that MTP may be a useful tool in characterizing pathways for promutagen activation.

Allyl Compounds↗
PubMed2006

Sub-chronic exposure to 1,1-dichloropropene induces frameshift mutations in lambda transgenic medaka.

1,1-Dichloropropene (1,1-DCP) is a contaminant present in both ground and surface waters used as sources for drinking water. Structural similarity to several compounds with known mutagenicity and carcinogenicity, and recent demonstration of mutagenicity in vitro, suggest this compound may be similarly mutagenic in vivo. A transgenic fish model, the lamda transgenic medaka, was used to evaluate the potential mutagenicity of this contaminant in vivo following sub-chronic exposure for 6 weeks. Mutant frequencies of the cII target gene (MF) increased six-fold in the livers of fish exposed to the lowest 1,1-DCP exposure concentration (0.44 mg/L, MF = 18.4 x 10(-5), and increased with each treatment, culminating in a 32-fold induction in fish from the highest 1,1-DCP treatment (16.60 mg/L, MF = 96.3 x 10(-5). Mutations recovered from treated fish showed a distinctive mutational spectrum comprised predominantly of +1 frameshift mutations, induced 166-fold above that of untreated animals. The majority of frameshifts were +1 insertions at thiamine and adenine. These results represent the first evidence of mutagenicity of 1,1-DCP in vivo, and of the highly characteristic spectrum of induced mutations dominated by +1 frameshift mutations. Based upon results from previous in vitro studies, the similar role of glutathione S-transferase (GSTT1-1) in the activation of 1,1-DCP to a mutagen in vivo is also suggested. This study further illustrates the utility of the lamda transgenic medaka as a model for identifying and characterizing potential genetic health risks associated with chemical exposures in the environment.

Allyl Compounds↗
PubMed2006

[Diallyl trisulfide induces apoptosis of human gastric cancer cell line MGC803 through caspase-3 pathway].

BACKGROUND & OBJECTIVE: Garlic and the organosulfer compound from garlic have antitumor effects, but the mechanisms still remain unclear. This study was to investigate the changes and significance of caspase-3 activity in diallyl trisulfide (DATS)-induced apoptosis of human gastric cancer cell line MGC803. METHODS: Effects of DATS on the apoptosis of MGC803 cells and the change of activated caspase-3 were observed under a fluorescent and an electron microscopy, and detected by flow cytometry and Western blot. RESULTS: After incubation with DATS, MGC803 cells showed typical apoptotic morphologic changes, and the apoptosis rate increased significantly. DATS activated caspase-3 in a time-dependent manner: the positive rates of activated caspase-3 were 1.9%, 3.0%, 7.3%, 14.4%, and 27.6% respectively in MGC-803 cells treated with 12 mg/L DATS for 0, 4, 8, 12 and 24 h. When treated with 12 mg/L DATS for 24 h, the apoptosis rate was significantly lower in the cells with pretreatment of Ac-DEVD-CHO (a caspase-3 inhibitor) than in the cells without pretreatment (5.1% vs. 23.0%, P<0.01), indicating that Ac-DEVD-CHO efficiently attenuated DATS-induced apoptosis of MGC803 cells. Moreover, pro-caspase-3 was hydrolyzed and activated in DATS-treated MGC803 cells. CONCLUSION: DATS induces apoptosis in MGC803 cells which may be through the activation of caspase-3 pathway.

Adenocarcinoma, Mucinous↗
PubMedDate not supplied

Effects of the garlic compounds diallyl sulphide and diallyl disulphide on arylamine N-acetyltransferase activity in Klebsiella pneumoniae.

Arylamine N-acetyltransferase (NAT) activities with 2-aminofluorene (2-AF) were determined in the bacterium Klebsiella pneumoniae. Cytosols or suspensions of K. pneumoniae with or without specific concentrations of diallyl sulphide (DAS) or diallyl disulphide (DADS) as co-treatment showed different percentages of 2-AF acetylation. The data indicated that there was decreased NAT activity associated with increased levels of DAS or DADS in K. pneumoniae. In growth studies on K. pneumoniae it was demonstrated that DAS or DADS elicited a dose-dependent bacteriocide effect on K. pneumoniae. For the cytosol examinations, the apparent values of Km and Vmax were 0.96+/-0.09 mM and 7.87+/-0.79 nmol min(-1) mg(-1) protein, respectively, for 2-AF. However, when DAS or DADS was added to the reaction mixtures, the apparent values of Km and Vmax were 0.16+/-0.04 mM and 0.99+/-0.16 nmol min(-1) mg(-1) protein with DAS, respectively, and 0.14+/-0.18 mM and 0.85+/-0.10 nmol min(-1) mg(-1) protein with DADS, respectively, for 2-AF. For the intact bacteria examination, the apparent values of Km and Vmax were 0.57+/-0.06 mM and 2.00+/-0.14 nmol min(-1) per 10x10(10) CFU, respectively, for 2-AF. However, when DAS or DADS was added to the reaction mixtures, the apparent of values of Km and Vmax were 0.41+/-0.04 mM and 1.30+/-0.10 nmol min(-1) per 10x10(10) CFU with DAS, respectively, and 0.34+/-0.04 mM and 1.08+/-0.08 nmol min(-1) per 10x10(10) CFU with DADS, respectively, for 2-AF. This report is the first demonstration to show that the garlic components DAS and DADS would affect K. pneumoniae growth and NAT activity.

2-Acetylaminofluorene↗
PubMed2004

Repetitive treatments of colon HT-29 cells with diallyl disulfide induce a prolonged hyperacetylation of histone H3 K14.

Diallyl disulfide (DADS) is a sulfur compound derived from garlic. Several studies carried out in rodents have revealed protective effects of DADS against colon carcinogenesis. The antipromoting effects of DADS may be partly related to its ability to inhibit tumoral cell proliferation. In a previous study, we have shown that in two human colon tumor cell lines (HT-29 and Caco-2) seeded at a low density (0.2 x 10(6) cells/100-mm petri dish), DADS antiproliferative effects were associated with a transient increase of histone H3 K14 acetylation. Moreover, DADS could inhibit nuclear histone deacetylase activity. Therefore, in the present study, we examined the possible effects of different experimental conditions (HT-29 cells at high density, repetitive treatments with DADS) on the pattern of DADS-induced histone hyperacetylation. Using HT-29 cells seeded at a higher density (5 x 10(6) cells/100-mm petri dish), we found that DADS induced histone H3 K14 hyperacetylation rapidly (3 h). When administrated as single treatments, the DADS effect on histone H3 K14 remained transient. In contrast, repetitive treatment with DADS resulted in a prolonged hyperacetylation of histone H3 K14. Whatever the cell culture conditions were, DADS had no effect on histone H4 acetylation. Thus, in vitro, the cell density and pattern of DADS treatment influenced the HT-29 nuclear response to DADS. DADS belongs to food-borne molecules that may play a role in chromatin remodeling and contribute to the nutritional modulation of gene expression.

Acetylation↗
PubMed1986

Chronic toxicology and carcinogenesis studies of Telone II by gavage in Fischer-344 rats and B6C3F1 mice.

Telone II (technical grade, 1,3-dichloropropene), a soil fumigant, was evaluated in chronic toxicology/carcinogenicity studies using Fischer-344 (F344) rats and B6C3F1 mice of both sexes. Doses administered were 0, 25, or 50 mg/kg to rats and 0, 50, or 100 mg/kg to mice. Telone II was given in corn oil by gavage 3 times per week for 104 wk. Ancillary studies were conducted to determine time-related effects, in which dose groups containing 5 male and 5 females rats were killed after receiving Telone II for 9, 16, 21, 24, or 27 mo. The primary organs affected were the forestomach (rats and mice), urinary bladder (mice), lung (mice), and liver (rats). Compound-related non-neoplastic lesions included basal-cell or epithelial hyperplasia of the forestomach (rats and mice), epithelial hyperplasia of the urinary bladder (mice), and hydronephrosis (mice). Neoplastic lesions associated with administration of Telone II included squamous-cell papillomas of the forestomach (male and female rats, female mice), squamous-cell carcinomas of the forestomach (Male rats, female mice), transitional-cell carcinomas of the urinary bladder (female mice), alveolar/bronchiolar adenomas (female mice), and neoplastic nodules of the liver (male rats). Although cis- and trans-1,3-dichloropropene are the principal components of Telone II, the presence of 1% epichlorohydrin, a direct-acting mutagen and carcinogen added as stabilizer, may have influenced the development of forestomach lesions. The results of the ancillary studies supported the findings of the carcinogenesis studies and demonstrated the time-dependent development of lesions in the forestomach (basal-cell hyperplasia and squamous-cell papilloma). Under the conditions of these gavage studies, Telone II was shown to be carcinogenic in male and female F344 rats and female B6C3F1 mice. Although the study in male B6C3F1 mice was considered inadequate because of the low survival resulting from suppurative inflammation of the heart (myocarditis) in the control group, there was some indication of Telone II-related increases of transitional-cell carcinomas of the urinary bladder, squamous-cell papillomas of the forestomach, and alveolar/bronchiolar adenomas and carcinomas of the lung.

Allyl Compounds↗
PubMed1999

Modulation of phase II enzymes by organosulfur compounds from allium vegetables in rat tissues.

The naturally occurring organosulfur compounds (OSCs) diallyl sulfide (DAS), diallyl disulfide (DADS), dipropyl sulfide (DPS), and dipropyl disulfide (DPDS) were studied with respect to their effects on hepatic, intestinal, renal, and pulmonary phase II drug metabolizing enzymes, i.e., glutathione S-transferase (GST), microsomal epoxide hydrolase (mEH), quinone reductase (QR), and UDP-glucuronosyltransferase (UGT). OSCs were administered po to male SPF Wistar rats. In addition to assays of total enzyme activity, the ability of OSCs to modify the levels of mEH and rGSTA1/A2, A3/A5, M1, M2, and P1 was assessed by Western blotting. Remarkably, DADS significantly increased all Phase II enzyme activities, except the pulmonary mEH. It was noteworthy that only DADS induced QR activity. DAS, DPS, and DPDS induced mEH, GST, and UGT activities in the liver. Interestingly, DAS, DPS, and DPDS significantly decreased renal GST activity. In the same manner, DAS, DPS, and DPDS decreased rGSTA1/A2 and A3/A5 levels in the kidney. Conversely, all OSCs were able to induce GST of alpha and mu classes in the liver. In the intestine, DADS and DAS increased rGSTA1/A2, M2, and P1, while rGSTA3/A5 and M2 were only increased by DADS. In addition, DADS induced rGSTP1 dramatically in the four tissues analyzed. DADS also increased the mEH levels in the liver, intestine, and kidney, while DAS and DPS moderately induced mEH level in the liver. This study brings additional insights into the effects of OSCs on Phase II enzymes and suggests that DADS could be a promising chemopreventive agent considering its pleiotropic capacity of induction.

Allium↗