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Transformation of chlororesorcinol by the hydrocarbonoclastic yeasts Candida maltosa, Candida tropicalis, and Trichosporon oivide.

The inhibitory effects of chlorinated monoaromatic compounds on three hydrocarbonoclastic yeasts grown on glucose or resorcinol were examined. At concentrations of 1.0 M, all of the monoaromatic compounds were inhibitory. When the concentration of chlororesorcinol was significantly reduced (0.0005 M), the inhibition to each yeast was minimized. Extracts of the cultures of yeasts growing on resorcinol plus chlororesorcinol were analyzed for residual resorcinol and chlororesorcinol with high pressure liquid chromatography. Neither compound was detected in the culture broth of Candida maltosa, but several unidentified compounds were present. Only chlororesorcinol was detected in the culture broth of Trichosporon oivide, and both resorcinol and chlororesorcinol were present in extract from cultures of C. tropicalis. Cultures of C. maltosa grown on resorcinol-yeast nitrogen base, washed and suspended in phosphate buffer and subsequently incubated with chlororesorcinol, turned the culture broth a distinct pink color. The data indicate that C. maltosa has the potential to co-metabolize chlororesorcinol.

Biotransformation↗

Experimental gluing of the bronchial stump after pneumonectomy in rats.

OBJECTIVE: The objective of this experimental study was to evaluate the usefulness of gelatin-resorcinol-dialdehyde adhesive in sutureless closure of bronchial stumps. METHODS: In 40 male Wistar rats bronchial stumps after left-sided pneumonectomy were closed by gluing with gelatin-resorcinol-dialdehyde adhesive. For macroscopic and microscopic examination four animals were sacrificed on postoperative days 2, 7 and 14 each, 14 animals on postoperative days 28 and 120 each. RESULTS: On macroscopic examination the gelatin-resorcinol-dialdehyde adhesive proved in all cases effective in tight bronchial stump closure. The adhesive did not cause local infection or necrosis of the bronchial stump nor other intrathoracic inflammatory complications. All animals survived and made an uncomplicated postoperative recovery. Microscopic examination revealed that the gelatin-resorcinol-dialdehyde adhesive initially evoked an acute inflammatory response with polymorphonuclear neutrophils predominating. After an intermediate stage characterized by a granulomatous reaction and resorption of the adhesive by multinucleated giant cells, 120 days postoperatively the bronchial stumps at the sites of previous gluing showed a regular fibrous scar tissue without inflammatory cells. CONCLUSION: The gelatin-resorcinol-dialdehyde adhesive showed effective in closing bronchial stumps after pneumonectomy in rats. The clinical extrapolation of this effect to thoracic surgical patients is uncertain at this time.

Animals↗

Beta 2-adrenoceptor selectivity in four series of beta-adrenoceptor agonists.

We studied the effect of two catechol and two resorcinol series of beta-adrenoceptor agonists on isolated papillary (beta 1-adrenoceptors) and soleus (beta 2-adrenoceptors) muscles preparations from the guinea-pig. One of the catechol and one of the resorcinol series were substituted by branched alkyl groups on the amino nitrogen, and the other two series were substituted by cycloalkyl groups. It was found that: the catechol derivatives were more potent than their corresponding resorcinol derivatives on both the papillary and the soleus muscle preparations, the resorcinol derivatives were more selective for the soleus muscle than their corresponding catechol derivatives, the substitution on the amino nitrogen gave compounds that were highly selective for the soleus muscle, both in the catechol and the resorcinol series. Greatest selectivity was obtained with a tertiary butyl group. the branched alkyl substitution on the amino nitrogen favoured selectivity for the soleus muscle more than cycloalkyl substitution did.

Adrenergic beta-Agonists↗

Cytokine release and cytotoxicity in human keratinocytes and fibroblasts induced by phenols and sodium dodecyl sulfate.

Phenolic compounds used in pharmaceutical and industrial products can cause irritant contact dermatitis. We studied the effects of resorcinol, phenol, 3,5-xylenol, chloroxylenol, and 4-hexyl-resorcinol on normal human epidermal keratinocytes and dermal fibroblasts for cytotoxicity and cytokine release, determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide methodology and enzyme-linked immunosorbent assay, respectively. An inverse correlation between phenol concentrations causing a 50% reduction in keratinocyte and fibroblast viability at 24 h and their octanol water-partition coefficients (i.e., hydrophobicity) was observed. 3,5-xylenol, chloroxylenol, hexyl-resorcinol, and sodium dodecyl sulfate, but not resorcinol or phenol, induced release of interleukin-1alpha from keratinocytes at cytotoxic concentrations. Variable release of tumor necrosis factor-alpha and interleukin-8 from keratinocytes occurred only at toxic threshold concentrations of the phenols or sodium dodecyl sulfate. Subtoxic concentrations of phenols or sodium dodecyl sulfate did not induce cytokine release from keratinocytes. Neither the phenols nor sodium dodecyl sulfate induced release of the chemokines interleukin-8, growth-related oncogene-alpha or monocyte chemotactic protein-1 from fibroblasts. Conditioned media from keratinocytes treated with cytotoxic concentrations of 3,5-xylenol, chloroxylenol, hexyl-resorcinol, or sodium dodecyl sulfate stimulated further release of the chemokines from fibroblasts above that obtained with control media. Rabbit anti-interleukin-1alpha serum inhibited keratinocyte-conditioned media induction of chemokine release. We have shown a structure-cytotoxicity relationship for a series of phenols as well as an association of interleukin-1alpha release with a cytotoxic effect. We demonstrated a cytokine cascade amplification step by the actions of stimulated keratinocyte media on cultured dermal fibroblasts, identifying interleukin-1alpha as the principal initiator of chemokine synthesis.

Cell Survival↗

Modification of hepato- and renal carcinogenesis by catechol and its isomers in rats pretreated with N-ethyl-N-hydroxyethylnitrosamine.

Modifying effects of catechol, resorcinol, and hydroquinone on second stage hepato- and renal carcinogenesis was investigated in rats pretreated with N-ethyl-N-hydroxyethyl-nitrosamine (EHEN). Groups of twenty 6-week-old Wistar/Crj male rats were treated with 0.1% EHEN in the drinking water for 3 weeks. Starting 1 week after the termination of EHEN treatment, they were given a diet containing 0.8% catechol, 0.8% resorcinol, or 0.8% hydroquinone or basal diet for 36 weeks. Further groups of 15 rats were each treated with the same doses of phenolic compounds or basal diet alone without EHEN pretreatment. All surviving animals were killed at the end of week 40 when histopathological assessment revealed significant reduction of the numbers per rat of hepatocellular adenomas and hepatocellular carcinomas by resorcinol, whereas hydroquinone significantly enhanced the numbers per rat of renal microadenomas and renal cell tumors. On the other hand, the number of alpha 2u-globulin positive tubules in the animals treated with hydroquinone was significantly lower than controls, without any alteration in bromodeoxyuridine (BrdU) incorporation. Lipid peroxidation, as evaluated by thiobarbituric acid reactive substance (TBARS), was at control levels in the kidneys of rats treated with hydroquinone throughout the experiment. The results showed that the known renal carcinogen hydroquinone potently enhances the second stage of EHEN-induced renal carcinogenesis, while its isomer resorcinol inhibited hepatocarcinogenesis. alpha 2u-Globulin and lipid peroxidation may not play roles in hydroquinone-associated promotion of renal carcinogenesis.

Adenoma↗

Anaerobic degradation of aniline and dihydroxybenzenes by newly isolated sulfate-reducing bacteria and description of Desulfobacterium anilini.

A new, rod-shaped, Gram-negative, non-sporing sulfate reducer (strain Ani1) was enriched and isolated from marine sediment with aniline as sole electron donor and carbon source. The strain degraded aniline completely to CO2 and NH3 with stoichiometric reduction of sulfate to sulfide. Strain Ani1 also degraded aminobenzoates and further aromatic and aliphatic compounds. The strain grew in sulfide-reduced mineral medium supplemented only with vitamin B12 and thiamine. Cells contained cytochromes, carbon monoxide dehydrogenase, and sulfite reductase P582, but no desulfoviridin. Strain Ani1 is described as a new species of the genus Desulfobacterium D. anilini. Marine enrichments with the three dihydroxybenzene isomers led to three different strains of sulfate-reducing bacteria; each of them could grow only with the isomer used for enrichment. Two strains isolated with catechol (strain Cat2) or resorcinol (strain Re10) were studied in detail. Both strains oxidized their substrates completely to CO2, and contained cytochromes, carbon monoxide dehydrogenase, and sulfite reductase P 582. Desulfoviridin was not present. Whereas the rod-shaped catechol oxidizer (strain Cat2) was able to grow on 18 aromatic compounds and several aliphatic substrates, the coccoid resorcinol-degrading bacterium (strain Re10) utilized only resorcinol, 2,4-dihydroxybenzoate and 1,3-cyclohexanedion. These strains could not be affiliated with existing species of sulfate-reducing bacteria. A further coccoid sulfate-reducing bacterium (strain Hy5) was isolated with hydroquinone and identified as a subspecies of Desulfococcus multivorans. Most-probable-number enumerations with catechol, phenol, and resorcinol showed relatively large numbers (10(4)-10(6) per ml) of aryl compound-degrading sulfate reducers in marine sediment samples.

Aniline Compounds↗

Studies of the mechanism of phenol hydroxylase: effect of mutation of proline 364 to serine.

An active site residue in phenol hydroxylase (PHHY), Pro364, was mutated to serine to investigate its role in enzymatic catalysis. In the presence of phenol, the reaction between the reduced flavin of P364S and oxygen is very fast, but only 13% of the flavin is utilized to hydroxylate the substrate, compared to nearly 100% for the wild-type enzyme. The oxidative half-reaction of PHHY using m-cresol as a substrate is similarly affected by the mutation. Pro364 was suggested to be important in stabilizing the transition state of the oxygen transfer step by forming a hydrogen bond between its carbonyl oxygen and the C4a-hydroperoxyflavin [Ridder, L., Mullholland, A. J., Rietjens, I. M. C. M., and Vervoort, J. (2000) J. Am. Chem. Soc. 122, 8728-8738]. The P364S mutation may weaken this interaction by increasing the flexibility of the peptide chain; hence, the transition state would be destabilized to result in a decreased level of hydroxylation of phenol. However, when the oxidative half-reaction was studied using resorcinol as a substrate, the P364S mutant form was not significantly different from the wild-type enzyme. The rate constants for all the reaction steps as well as the hydroxylation efficiency (coupling between NADPH oxidation and resorcinol consumption) are comparable to those of the wild-type enzyme. It is suggested that the function of Pro364 in catalysis, stabilization of the transition state, is not as important in the reaction with resorcinol, possibly because the position of hydroxylation is different with resorcinol than with phenol and m-cresol.

Amino Acid Substitution↗

Experimental gluing of lung parenchyma in rats.

Gelatin-resorcinol-dialdehyde adhesive has been developed from a gelatin-resorcinol-formaldehyde adhesive by replacing the formaldehyde with two less histotoxic dialdehydes, ethandial and pentandial. The aim of the present study was to evaluate the usefulness of this modified composition in gluing defects in lung parenchyma. In 40 male Wistar rats a standardized lung incision 1.0 cm in length and 0.8 cm in depth were closed by application of gelatin-resorcinol-dialdehyde adhesive. For macroscopic and microscopic examination 4 animals were sacrificed on each of postoperative days 2, 7, and 14 and 14 animals on each of postoperative days 28 and 120. Macroscopic examination revealed a tight closure of the parenchymal defects in all postoperative stages. Initially by an adhesive layer and later on by granulation tissue and scar tissue respectively. On microscopic examination an inflammatory tissue response with polymorphonuclear neutrophils and macrophages predominating was found 2 days postoperatively. After 7 days multinucleated giant cells appeared. On postoperative day 14 the tissue response presented a distinct granulomatous character with multinucleated giant cells persisting. After 28 days remnants of adhesive surrounded by granulation tissue were detectable. On postoperative day 120 the adhesive had been completely resorbed and the parenchymal defect was replaced by fibrous scar tissue. The gelatin-resorcinol-adhesive proved effective in tight closure of lung parenchyma in rats. The adhesive is resorbed completely and does not interfere with parenchymal healing.

Absorption↗

Flow injection chemiluminescence analysis of phenolic compounds using the NCS-luminol system.

A flow injection system coupled with two simple and sensitive chemiluminescence (CL) methods is described for the determination of some phenolic compounds. The methods are based on the inhibition effects of the investigated phenols on the CL signal intensities of N-chlorosuccinimide-KI-luminol (NCS-KI-luminol) and NCS-luminol systems. The influences of the chemical and hydrodynamic parameters on the decrease in CL signal intensities of NCS-KI-luminol and NCS-luminol systems for hydroquinone, catechol, and resorcinol, serving as the model compounds of analyte, were studied in the flow injection mode of analysis. Under the selected conditions, the proposed CL systems were used for the determination of some phenolic compound and analytical characteristics of the systems including calibration equation, correlation coefficient, linear dynamic range, limit of detection, and sample throughput. The limits of detection for hydroquinone, catechol, and resorcinol were 0.002, 0.01, and 0.3 microM using the NCS-KI-luminol system; for the NCS-luminol system these were 0.01, 0.17, and 1.6 microM, respectively. The relative standard deviation for 10 repeated measurements of 0.04, 0.06, and 1 microM of hydroquinone, catechol, and resorcinol were 1.9, 1.4, and 2.0%, respectively, with the NCS-KI-luminol system; for 0.2, 0.5, and 4 microM of hydroquinone, catechol, and resorcinol these were 2.6, 2.2, and 3.7%, respectively, using the NCS-luminol system. The method was applied to the determination of catechol in known environmental water samples with a relative error of less than 6%. A possible reaction mechanism of the proposed CL system is discussed briefly.

Catechols↗

The production of viral RNA inactivator(s) from the interaction of dihydric and trihydric phenols with cupric ion.

Eight lots of reagent-grade phenol from four companies were tested for capacity to interact with Cu2+ to produce an inactivator or inactivators of the transfective RNA obtained from poliovirions; such capacity to interact with Cu2+ is referred to as cofactor activity. Six of the lots showed cofactor activity; two did not. A review of the data on the phenol lots and of the properties of the impurity or impurities conferring cofactor activity suggested that the active impurity(ies) might be a dihydric or trihydric phenol. Commercial catechol, resorcinol, hydroquinone, orcinol and pyrogallol were tested and found active. The activity of hydroquinone was outstandingly high. Upon serial recrystallization, the activity of catechol, hydroquinone, orcinol and pyrogallol remained constant, but the activity of resorcinol decreased markedly, in stepwise fashion, showing the most of the activity of the commercial resorcinol was due to impurity(ies). Each of catechol, hydroquinone, orcinol, pyrogallol, and the commercial resorcinol was shown to react with Cu2+ to produce inactivator(s). The effective target for inactivator(s) was the RNA and not the transfection process. The kinetics of inactivator(s) production varied for the different phenols, and the inactivator activity of the incubated mixture of pyrogallol and Cu2+ was notably labile.

Copper↗

Effects of phenols on eicosanoid synthesis in A23187-stimulated human whole blood.

We have previously demonstrated that catecholamines have opposite effects on leukotriene (LT) and prostanoid synthesis. The aim of the present study was to test the effects of phenols (catechol, hydroquinone, phenol and resorcinol) on LTB4, LTE4 and thromboxane (TX)B2 synthesis in A23187-stimulated human whole blood. All tested compounds inhibited LTB4 and LTE4 synthesis. The IC50 values for catechol were 3 microM, 6 microM; for hydroquinone 4 microM, 3 microM; for phenol 285 microM, 226 microM and for resorcinol 180 microM, 902 microM. The compounds did not stimulate TXB2 synthesis but only inhibited it. The IC50 value for catechol was 3 microM, for hydroquinone 7 microM, for phenol 18 microM and for resorcinol 25 microM. Catechol and hydroquinone had hardly any effect on the LT/TX ratio. Phenol and resorcinol even increased the LT/TX ratio. The positions of hydroxyl groups of phenolic compounds are thus important for their actions on the LT/TX ratio.

Calcimycin↗

Deoxygenation of polyhydroxybenzenes: an alternative strategy for the benzene-free synthesis of aromatic chemicals.

New synthetic connections have been established between glucose and aromatic chemicals such as pyrogallol, hydroquinone, and resorcinol. The centerpiece of this approach is the removal of one oxygen atom from 1,2,3,4-tetrahydroxybenzene, hydroxyhydroquinone, and phloroglucinol methyl ether to form pyrogallol, hydroquinone, and resorcinol, respectively. Deoxygenations are accomplished by Rh-catalyzed hydrogenation of the starting polyhydroxybenzenes followed by acid-catalyzed dehydration of putative dihydro intermediates. Pyrogallol synthesis consists of converting glucose into myo-inositol, oxidation to myo-2-inosose, dehydration to 1,2,3,4-tetrahydroxybenzene, and deoxygenation to form pyrogallol. Synthesis of pyrogallol via myo-2-inosose requires 4 enzyme-catalyzed and 2 chemical steps. For comparison, synthesis of pyrogallol from glucose via gallic acid intermediacy and the shikimate pathway requires at least 20 enzyme-catalyzed steps. A new benzene-free synthesis of hydroquinone employs conversion of glucose into 2-deoxy-scyllo-inosose, dehydration of this inosose to hydroxyhydroquinone, and subsequent deoxygenation to form hydroquinone. Synthesis of hydroquinone via 2-deoxy-scyllo-inosose requires 2 enzyme-catalyzed and 2 chemical steps. By contrast, synthesis of hydroquinone using the shikimate pathway and intermediacy of quinic acid requires 18 enzyme-catalyzed steps and 1 chemical step. Methylation of triacetic acid lactone, cyclization, and regioselective deoxygenation of phloroglucinol methyl ether affords resorcinol. Given the ability to synthesize triacetic acid lactone from glucose, this constitutes the first benzene-free route for the synthesis of resorcinol.

Journal Article↗

Self-assembly of silver nanoparticles: synthesis, stabilization, optical properties, and application in surface-enhanced Raman scattering.

Silver nanoparticle aggregates were synthesized in large scale using resorcinol under alkaline condition to obtain an assembly of silver clusters. Stable dispersion of the cluster in aqueous medium has been examined out of resorcinol-capped silver nanoparticle assemblies. The UV-vis spectroscopy during the particle evolution has been studied in detail. From the high-resolution TEM (HRTEM) image and XRD pattern it was confirmed that the particles are made of pure silver only. The capping action of resorcinol has been authenticated from the FTIR spectra. UV-vis spectroscopy and TEM images reveal that the temperature, effect of vibrational energy, heat shock, and time-dependent particle evolution have unique bearing on the stability and surface properties of the clusters. The concentrations of silver nitrate, resorcinol, and NaOH have important influence on the particle evolution and its size. TEM images incite us to examine the aggregates to capitulate surface-enhanced Raman scattering (SERS) to the single molecular level using crystal violet (CV) and cresyl fast violet (CFV) as molecular probes. The SERS intensity of CV increases with increasing the size of the silver aggregate.

Metal Nanoparticles↗

The role of GSH depletion and toxicity in hydroquinone-induced development of enzyme-altered foci.

Hydroquinone (HQ) may activate oxygen via redox cycles in biological systems and may also deplete glutathione (GSH). Both these reactions are potentially harmful, and we have studied their possible involvement in hydroquinone-induced development of gamma-glutamyltranspeptidase (GGT)-positive enzyme-altered foci in rat liver. The effect of HQ was compared to the effect of duroquinone, catechol, resorcinol and phenol. The dose was 100 mg/kg per day and the test substances were administered for 7-12 weeks in these foci experiments. HQ gave an increased number of foci and increased the foci volume, while none of the other compounds had any significant effect on these parameters. HQ, duroquinone and resorcinol were also tested at a higher dose level (200 mg/kg per day), but this dose gave a lower number of foci than the 100-mg dose. HQ, duroquinone and catechol induced single-strand breaks in hepatic DNA. Single doses of HQ (200 mg/kg) increased malondialdehyde excretion in urine, indicating in vivo lipid peroxidation. Duroquinone, phenol and resorcinol were negative with respect to malondialdehyde excretion. Catechol could not be properly tested as the 200-mg dose killed several animals. HQ and catechol induced hepatic ornithine decarboxylase activity. This effect was correlated to GSH depletion. An in vitro model for toxicity studies with hepatocytes from carcinogen-treated rats was also used. In this model HQ could be shown to be selectively toxic to GGT-negative cells in the presence of extracellular GSH. The toxicity was preceded by a rapid depletion of GSH. Catechol also depleted GSH and could be shown to be selectively toxic, but higher concentrations than those used for HQ had to be used. Duroquinone, phenol and resorcinol were not selectively toxic to GGT-negative cells. As duroquinone can be regarded as a more potent inducer of redox cycles than HQ, it can be concluded that the foci data provide no evidence for an involvement of redox cycles in HQ induced development of enzyme-altered foci. They suggest that GSH depletion may act to develop enzyme-altered foci, and the in vitro data indicate a mechanism by which GSH depletion and toxicity may induce this effect.

Animals↗

Potency and selectivity in vitro of compounds related to isoprenaline and orciprenaline on beta-adrenoceptors in the guinea-pig.

1 Amines related in structure to either isoprenaline (catechol series) or orciprenaline (resorcinol series) were examined for activity on isolated trachea (relaxation), atria (chronotropic action) and perfused hind-limb (vasodilatation) of the guinea-pig.2 Compounds with a resorcinol nucleus were less potent on all three preparations but more selective for trachea than were compounds with a catechol nucleus.3 In both catechol and resorcinol compounds potency on trachea was enhanced by and selectivity for trachea was favoured by substitution of a p-OH phenyl group in the N-iso propyl, or by replacement of the N-iso propyl with an N-t-butyl, with or without a p-OH phenyl group.4 Most of the compounds, particularly the resorcinols, had much lower potencies, relative to isoprenaline, on hind-limb than on trachea.5 Some of the problems associated with the quantitative measurement of selectivity and with sub-classification of beta-adrenoceptors are discussed.

Animals↗

Thermophilic, reversible gamma-resorcylate decarboxylase from Rhizobium sp. strain MTP-10005: purification, molecular characterization, and expression.

We found the occurrence of thermophilic reversible gamma-resorcylate decarboxylase (gamma-RDC) in the cell extract of a bacterium isolated from natural water, Rhizobium sp. strain MTP-10005, and purified the enzyme to homogeneity. The molecular mass of the enzyme was determined to be about 151 kDa by gel filtration, and that of the subunit was 37.5 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis; in other words, the enzyme was a homotetramer. The enzyme was induced specifically by the addition of gamma-resorcylate to the medium. The enzyme required no coenzyme and did not act on 2,4-dihydroxybenzoate, 2,5-dihydroxybenzoate, 3,4-dihydroxybenzoate, 3,5-dihydroxybenzoate, 2-hydroxybenzoate, or 3-hydroxybenzoate. It was relatively thermostable to heat treatment, and its half-life at 50 degrees C was estimated to be 122 min; furthermore, it catalyzed the reverse carboxylation of resorcinol. The values of k(cat)/K(m) (mMu(-1) . s(-1)) for gamma-resorcylate and resorcinol at 30 degrees C and pH 7 were 13.4 and 0.098, respectively. The enzyme contains 327 amino acid residues, and sequence identities were found with those of hypothetical protein AGR C 4595p from Agrobacterium tumefaciens strain C58 (96% identity), 5-carboxyvanillate decarboxylase from Sphingomonas paucimobilis (32%), and 2-amino-3-carboxymuconate-6-semialdehyde decarboxylases from Bacillus cereus ATCC 10987 (26%), Rattus norvegicus (26%), and Homo sapiens (25%). The genes (graA [1,230 bp], graB [888 bp], and graC [1,056 bp]) that are homologous to those in the resorcinol pathway also exist upstream and downstream of the gamma-RDC gene. Judging from these results, the resorcinol pathway also exists in Rhizobium sp. strain MTP-10005, and gamma-RDC probably catalyzes a reaction just before the hydroxylase in it does.

Amino Acid Sequence↗

Endemic goiter in western Colombia.

Goiter continues to occur in some areas of western Colombia despite iodine supplementation for 30 years. In 1973-1977, an average goiter prevalence of 15% (range 1-42%) still persisted among schoolchildren of 41 localities. Significant relationships were found between goiter prevalence and both the geological composition of watersheds and bacterial contamination of water supplies. Together, these associations account for 80% of the observed variation in goiter prevalence. The presence of sedimentary rocks rich in organic matter (coals, shales, etc.) was the best indicator of disease. The second best indicator, presence of K. pneumoniae in the water source, was associated with lower goiter prevalence but, as in other investigations, contamination of the pipeline system (households and schools) with gram-negative bacteria was associated with higher disease rates. Thus, epidemiological evidence indicates a cause-effect relationship between sources of drinking water and the persistence and development of goiter in this part of the world. Furthermore, identification of resorcinol, phthalate esters, and sulfur-bearing organic compounds, possibly aliphatic disulfides, in the water supplying the endemic goiter district of Candelaria town in western Colombia adds experimental support to this hypothesis. Resorcinol is derived from coal and humic substances, high molecular weight complex polymeric organic compounds present in sedimentary rocks, soils and water. Resorcinol is goitrogenic in man and experimental animals. Phthalate esters, also related to humic materials, undergo biodegradation by gram-negative bacteria with production of intermediate metabolites possessing antithyroid activity. Like phthalates and resorcinol, organic disulfides have also been identified as water contaminants in other parts of the world, and are known to be potent antithyroid compounds. The goitrogenic effect of organic and bacterial pollutants in water supplies is more pronounced in segments of the population with dietary iodine deficiency--as seen prior to the iodine prophylaxis program--and/or poor socio-economic conditions. Studies are underway to provide both insight into the biogeochemical cycle of water-borne goitrogens and knowledge essential to the development of rapid, inexpensive, and precise methods for detecting and quantifying the offending agents, as well as devising effective sanitation techniques for their inactivation and/or elimination. The impact of such measures will be determined on goiter prevalence and other parameters of health and nutrition of the communities under study.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Induction of phenol-metabolizing enzymes in Trichosporon cutaneum.

Some aspects of the induction of enzymes participating in the metabolism of phenol and resorcinol in Trichosporon cutaneum were studied using intact cells and cell-free preparations. Activities of phenol hydroxylase (1.14.13.7), catechol 1,2-oxygenase (1.13, 11.1), cis-cis-muconate cyclase (5.5.1.-), delactonizing enzyme(s) and maleolylacetate reductase were 50-400 times higher in fully induced cells than in noninduced cells. In addition to phenol and resorcinol, also catechol, cresols and fluorophenols could induce phenol hydroxylase. The induction was severely inhibited by phenol concentrations higher than 1 mM. Using optimum inducer concentrations (0.01-0.10 mM), it took more than 8 h to obtain full induction, whether in proliferating or in nonproliferating cells. Phenol hydroxylase, catechol 1,2-oxygenase and cis, cis-muconate cyclase were induced simultaneously. The synthesis of the de-lactonizing activity was delayed in relation to these three preceeding enzymes of the pathway. High glucose concentration (over 15 mM) inhibited completely the induction of phenol oxidation by nonproliferating cells. It also inhibited phenol oxidation by pre-induced cells. Among the NADPH-generating enzymes, the activity of iso-citrate dehydrogenase was elevated in cells grown on phenol and resorcinol instead of glucose.

Catechol 1,2-Dioxygenase↗