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1.
N-Substituted aromatic compounds are environmental contaminants associated with the production and use of dyes, explosives, pesticides and pharmaceuticals. In this article, we examine the potential of anaerobic granular sludge from anaerobic treatment systems towards the detoxification, transformation, and mineralization of nitroaromatic and azo compounds. Nitroaromatics and azo dyes with strong electron withdrawing are highly inhibitory to acetoclastic methanogenic bacteria. However, nitro and azo substituted aromatics are readily reductively detoxified in methanogenic consortia to their respective aromatic amines, which are several orders of magnitude less toxic. This reductive detoxification has allowed the successful operation of anaerobic reactors for the treatment of highly toxic aromatic compounds. In the course of the experiments it was discovered that some aromatic amines were mineralized. These results indicate that some N-substituted aromatic compounds can be completely mineralized and serve as a carbon and energy source for anaerobic bacteria.  相似文献   

2.
The relative toxicity (log IGC50(-1)) of 49 selected aliphatic amines and aminoalkanols was evaluated in the static Tetrahymena pyriformis population growth impairment assay. Excess toxicity, indicated by potency greater than predicted for non-polar narcotic alkanols, was associated with both classes of test chemicals. Moreover, the aminoalkanols were found to be more toxic than the corresponding alkanamines. A high quality 1-octanol/water partition coefficient (log K(ow)) dependent quantitative structure-activity relationship (QSAR), logIGC50(-1) = 0.78 (log K(ow)) - 1.42; r2 = 0.934, was developed for alkanamines. This QSAR represented the amine narcosis mechanism of toxic action. No quality QSAR was developed for the aminoalkanols. However, several structure-toxicity features were observed for this class of chemicals. Two-amino-1-hydroxy derivatives being more toxic than the corresponding derivatives, where the amino and hydroxy moieties were separated by methylene groups. Hydrocarbon branching next to the amino moiety resulted in decreased toxicity. Aminoalkanol alters lipid metabolism in T. pyriformis.  相似文献   

3.
For many acute-acting chemicals, toxic responses observed in vivo correlate strongly with metabolic activation and macromolecular covalent binding (CVB) observed in vitro and often in vivo; bromobenzene (BB) is a classic example of this behavior. Substituent groups modulate the toxicity of bromobenzene in vivo and in liver slices cultured in vitro in parallel fashion [Fisher, R., Hanzlik, R.P., Gandolfi, J.A., and Brendel, K. (1992), In Vitro Toxicology, 4, 173-186]. In the present study we used the liver slice system to examine the relationship between toxicity, metabolism and covalent binding amongst a series of [3H/14C] dual labelled BB derivatives including (in order of increasing hepatotoxicity) o-bromoanisole (BA), o-bromotoluene (BT), o-bromobenzonitrile (BBN), BB and o-dibromobenzene (DBB). Among these congeners apparent relative rates of metabolism varied only 4-fold, but the most extensively metabolized compounds were the least toxic. CVB varied 7-fold across the series, and those compounds which bound the most frequently were the most toxic. For each compound the relative binding index (RBI = pmol bound/nmol metabolized) and the average retention of tritium relative to carbon-14 in the CVB fraction were constant throughout the 24 h incubations, suggesting that the metabolic profile of each compound remained constant with time. The RBI values, however, did not reflect relative toxicity as well as total CVB values. The T/C ratios of the CVB residues varied from 0.36 (for BA) to 0.81 (for BBN), indicating that ortho-substitution on BB exerts important qualitative as well as quantitative effects on overall metabolism and reactive metabolite formation. The finding that relative toxicity among a series of bromobenzene congeners is paralleled by their relative covalent binding measured in the same system in which toxicity is assessed adds support to the hypothesis that covalent binding contributes to the observed toxicity, rather than merely being a correlated epiphenomenon.  相似文献   

4.
In connection with the development of new anticonvulsant agents with a broad spectrum, we found that N-Cbz-alpha-amino-N-alkylsuccinimides showed significant anticonvulsant activities, and the pharmacological activities of these compounds were dependent on their stereochemistry and N-substituted alkyl group. These results prompted us to define the effects of other functional group on the anticonvulsant activities of these compounds. Therefore a series of N-alkoxycarbonyl-alpha-amino-N-methylsuccinimide were prepared from N-Cbz-aspartic acid and were evaluated with their anticonvulsant activities against the MES and PTZ tests, in order to define the effect of N-substituted alkoxy carbonyl group with the anticonvulsant activities. From these studies, it was found that all the tested N-alkoxycarbonyl-alpha-amino-N-methylsuccinimides exhibited significant anticonvulsant activities in the PTZ test and were not active in the MES test. The most active compound in the PTZ test was (S) N-ethoxycarbonyl-alpha-amino-N-methyl-succinimide. We found that the pharmacological activities in the PTZ test were dependent on their N-alkoxycarbonyl groups. They follow as such; The order of anticonvulsant activities for (R) series as evaluated by ED50 was N-phenoxycarbonyl = N-4-nitrobenzyloxycarbonyl > N-ethoxycarbonyl > N-allyloxycarbonyl > N-tert. butoxycarbonyl compound; For the (S) series N-ethoxycarbonyl > N-phenoxycarbonyl > N-allyloxycarbonyl compound. From the above results, it was conceivable that N-substituted alkoxycarbonyl group had certain effects on the anticonvulsant activities of N-alkoxycarbonyl-alpha-amino-N-methylsuccinimides.  相似文献   

5.
Analogues of purine nucleosides and deoxynucleosides were tested for toxicity against the intraerythrocytic parasite Plasmodium falciparum in vitro culture. Sangivamycin (7-deaza-7-amido-adenosine) (IC37 of 0.3 microM), tubercidin (7-deaza-adenosine) (IC37 of 0.7 microM), 6-methylamino-deoxyadenosine (IC37 of 10 microM), 8-aza-2-amino-deoxy-adenosine (IC37 of 11 microM) and 2-chloro-adenosine (IC37 of 11 microM) were found to be the most toxic towards the parasite. Structure-activity analysis suggested that alteration of the purine ring at the 7 or 8 position significantly increased the toxicity of the compound against P. falciparum. Analysis by HPLC of parasite lysates which had been subjected to the cytotoxic compounds confirmed that alterations in the flux of the purine salvage pathways of the parasite had occurred. Comparison of the toxicity of these compounds against P. falciparum with the toxicity against a similar intraerythrocytic parasite, Babesia bovis, or human melanoma cell lines indicated a differential toxicity, in that many of the compounds toxic towards P. falciparum were relatively non-toxic towards human melanoma cell lines or B. bovis and vice versa. The mechanism of toxicity of the deoxyadenosine and adenosine analogues, whose normal metabolism involves transport, metabolism and incorporation into nucleic acids appears to vary significantly between P. falciparum, B. bovis and mammalian cells.  相似文献   

6.
One of the most problematic groups of the USEPA and EU priority pollutants are the halogenated organic compounds. These substances have a wide range of industrial applications, such as solvents and cleaners. Inadequate disposal techniques and accidental spillages have led to their detection in soil, groundwater, and river sediments. Persistence of these compounds in the environment has resulted from low levels of biodegradation due to chemical structural features that preclude or retard biological attack. Research has indicated the idea that treatment systems based on methanotrophic co-metabolic transformation may be a cost-effective and efficient alternative to physical methods because of the potential for high transformation rates, the possibility of complete compound degradation without the formation of toxic metabolites, applicability to a broad spectrum of compounds, and the use of a widely available and inexpensive growth substrate. A substantial amount of work concerning methanotrophic cometabolic transformations has been carried out using the soluble form of methane monooxygenase (sMMO) from the obligate methanotroph Methylosinus trichosporium OB3b. This NADH-dependent monooxygenase is derepressed when cells are grown under copper stress. sMMO has a wider specificity than the particulate form. sMMO has been shown to degrade trichloroethylene (TCE) at a rate of at least one order of magnitude faster than obtained with other mixed and pure cultures, suggesting it has a wider application to bioremediation. Furthermore, sMMO catalyzes an unusually wide range of oxidation reactions, including the hydroxylation of alkanes, epoxidation of alkenes, ethers, halogenated methanes, cyclic and aromatic compounds including compounds, that are resistant to degradation in the environment. However, the practical application of methantrophs and Methylosinus trichosporium OB3b to the treatment of chlorinated organics has met with mixed success. Although oxidation rates are rapid, compound oxidation with M. trichosporium OB3b is difficult. This fastidious organism grows relatively slowly, which limits the speed with which sMMO expressing biomass can be generated. Furthermore, product toxicity toward the cell, affecting the stability of the enzyme when transforming certain compounds has been observed, for example, by the products of 1,2,3 trichlorobenzene hydroxylation (2,3,4- and 3,4,5-trichlorophenol) and of TCE degradation (chloral hydrate). Because of this toxicity and the inability of sMMO to further oxidize its own hydroxylation products, the ability of methane monoxygenase to carry out the monooxygenation of a wide variety of substituted aromatics and polyaromatics cannot be fully exploited in M. trichosporium OB3b. Many of these problems could be overcome by the use of either a mixed downstream heterotrophic population of organisms that could accommodate the products of hydroxylation or to express sMMO in an organism that could metabolize the products of hydroxylation. The latter of these two approaches would have several advantages. The main benefit would be the removal of the need for methane, which is required to induce sMMO in M. trichosporium OB3b, and supply carbon and energy to the cells that continuously oxidise the target compound, but also acts as a competitive inhibitor of sMMO. Instead, the recombinant could utilize the products of sMMO-mediated hydroxylation as a carbon source.  相似文献   

7.
Atom/fragment contribution values, used to estimate the log octanol-water partition coefficient (log P) of organic compounds, have been determined for 130 simple chemical substructures by a multiple linear regression of 1120 compounds with measured log P values. An additional 1231 compounds were used to determine 235 "correction factors" for various substructure orientations. The log P of a compound is estimated by simply summing all atom/fragment contribution values and correction factors occurring in a chemical structure. For the 2351 compound training set, the correlation coefficient (r2) for the estimated vs measured log P values is 0.98 with a standard deviation (SD) of 0.22 and an absolute mean error (ME) of 0.16 log units. This atom/fragment contribution (AFC) method was then tested on a separate validation set of 6055 measured log P values that were not used to derive the methodology and yielded an r2 of 0.943, an SD of 0.408, and an ME of 0.31. The method is able to predict log P within +/- 0.8 log units for over 96% of the experimental dataset of 8406 compounds. Because of the simple atom/fragment methodology, "missing fragments" (a problem encountered in other methods) do not occur in the AFC method. Statistically, it is superior to other comprehensive estimation methods.  相似文献   

8.
A three-dimensional cell culture system was used as a model to study the influence of low levels of mercury in the developing brain. Aggregating cell cultures of fetal rat telencephalon were treated for 10 days either during an early developmental period (i.e., between days 5 and 15 in vitro) or during a phase of advanced maturation (i.e., between days 25 and 35) with mercury. An inorganic (HgCl2) and an organic mercury compound (monomethylmercury chloride, MeHgCl) were examined. By monitoring changes in cell type-specific enzymes activities, the concentration-dependent toxicity of the compounds was determined. In immature cultures, a general cytotoxicity was observed at 10(-6) M for both mercury compounds. In these cultures, HgCl2 appeared somewhat more toxic than MeHgCl. However, no appreciable demethylation of MeHgCl could be detected, indicating similar toxic potencies for both mercury compounds. In highly differentiated cultures, by contrast, MeHgCl exhibited a higher toxic potency than HgCl2. In addition, at 10(-6) M, MeHgCl showed pronounced neuron-specific toxicity. Below the cytotoxic concentrations, distinct glia-specific reactions could be observed with both mercury compounds. An increase in the immunoreactivity for glial fibrillary acidic protein, typical for gliosis, could be observed at concentrations between 10(-9) M and 10(-7) M in immature cultures, and between 10(-8) M and 3 x 10(-5) M in highly differentiated cultures. A conspicuous increase in the number and clustering of GSI-B4 lectin-binding cells, indicating a microglial response, was found at concentrations between 10(-10) M and 10(-7) M. These development-dependent and cell type-specific effects may reflect the pathogenic potential of long-term exposure to subclinical doses of mercury.  相似文献   

9.
The purpose of this study was to examine the possibility of using Artemia salina as a test organism in the search for compounds having the ability to protect against superoxide-mediated toxicity. The basic procedure for the assay using Artemia salina was performed as described in previous literature, with minor modifications. We found that Artemia salina are extremely sensitive to menadione bisulfite, a compound whose toxicity is probably mediated by intracellular superoxide generation. Desferrioxamine (desferal), a compound with known protective effects, was shown to display dramatic protective activity in our system. We also observed that an inhibitor of endogenous superoxide dismutase (SOD) activity increased the toxicity of menadione toward Artemia salina. In conclusion, this simple, inexpensive, and convenient assay could be a valuable addition to a screening effort in the search for compounds that will be protective against damage by superoxide or other active oxygen species.  相似文献   

10.
The COMPACT approach for defining structural criteria for substrates and inducers of cytochrome P450 (CYP) enzymes which mediate the formation of reactive intermediates is discussed in the context of prediction of potential carcinogenicity. This is broadened to encompass structural studies on mammalian P450s, including those relevant to genetic polymorphism in man. The use of the COMPACT system, in parallel with the structure alert program HazardExpert (now incorporated into the Pallas system), for evaluating human carcinogenicity data is reported, as an example of the possible employment of a battery of short-term test procedures for safety evaluation. In particular, the importance of using the log P value (as a measure of compound lipophilicity) to assess the likelihood of a potentially toxic compound reaching the site of activation, is emphasized by the finding that most procarcinogens requiring metabolic activation by P450s are lipophilic in nature.  相似文献   

11.
Ethical practice in managed care: a dose of realism   总被引:1,自引:0,他引:1  
"Animal-Plant Warfare" is one of the hypotheses for the evolution of drug-metabolizing P450s. To address the validity of this hypothesis, we examined the induction of xenobiotic-metabolizing P450s by 12 plant toxins in rats, using hepatic activity for testosterone metabolism as the index. The compounds tested were aconitine, morphine, tubocurarine, physostigmine, pilocarpine, muscarine, cocaine, atropine, amygdalin, digitonin, nicotine and solanine. Drinking water containing a test compound was given to rats for 4 days, and the hepatic activity of testosterone metabolism was determined together with monitoring body weight gain and liver weight as the indices of toxicity. The results showed that while cocaine and nicotine have a minor ability to increase testosterone 16 beta-hydroxylase activity, a marker activity for the CYP2B1 and 2, all other compounds did not have any such effect. No correlation was observed between a change in 16 beta-hydroxylase and toxicity caused by toxins. Therefore, these results did not support the idea that the inducibility of the CYP2B subfamily in animals is acquired through "Animal-Plant Warfare". Several compounds examined here increased or decreased hepatic activities of testosterone 2 alpha-, 6 beta-, 7 alpha- and 16 alpha-hydroxylation and 17-oxidation, indicating a possible effect on the CYP2A, 2C and 3A subfamily. Of these effects, a moderate correlation (r < 0.49) was observed in the changes in the activities of 2 alpha-/16 alpha-hydroxylation and 17-oxidation vs. that in toxicity. It is therefore suggested that inhibition or suppression of the expression of CYP2C11 is one of the mechanisms in the toxicity of plant toxins for rats, although it comes from an examination using limited numbers of compounds.  相似文献   

12.
Synthetic organic colorants, the majority of which are recalcitrant in nature, are used universally in many different manufacturing processes. The dyes are released into the environment in industrial effluents and are highly visible even at low concentrations (<1 mg∕L). Added to this, certain dyes, dye precursors, and aromatic amines have been shown to be carcinogenic. Thus, appropriate treatment of dye wastewaters to remove color and the dye compounds is clearly an important issue. Methanogenic toxicity tests on several food dyes provided a range of toxicity results, from noninhibitory (IC50 >20 g∕L) to inhibitory (IC50 0.2 mg∕L). Batch biodegradability assays indicated that the dyes were not readily utilized by the anaerobic microorganisms as a sole substrate. Decolorization of the dye tartrazine was investigated in a laboratory-scale anaerobic baffled reactor at a concentration of 250 mg∕L. Reduction in COD of 50–60% and color reduction of about 95% was achieved. Initially the tartrazine was not readily decolorized; however, decolorization improved with acclimation of the biomass. An industrial wastewater from a food dye manufacturer was fed to a second laboratory-scale anaerobic baffled reactor at a concentration of 5% (volume-to-volume ratio) and then increased to 10% (volume-to-volume ratio). Anaerobic degradation of the wastewater was efficient. Methanogenic activity was high; the organic content of the influent was reduced by about 70%, and color was reduced by almost 90%  相似文献   

13.
Our review of the metabolic pathways of pyridines and aza-arenes showed that biodegradation of heterocyclic aromatic compounds occurs under both aerobic and anaerobic conditions. Depending upon the environmental conditions, different types of bacteria, fungi, and enzymes are involved in the degradation process of these compounds. Our review indicated that different organisms are using different pathways to biotransform a substrate. Our review also showed that the transformation rate of the pyridine derivatives is dependent on the substituents. For example, pyridine carboxylic acids have the highest transformation rate followed by mono-hydroxypyridines, methylpyridines, aminopyridines, and halogenated pyridines. Through the isolation of metabolites, it was possible to demonstrate the mineralization pathway of various heterocyclic aromatic compounds. By using 14C-labeled substrates, it was possible to show that ring fission of a specific heterocyclic compound occurs at a specific position of the ring. Furthermore, many researchers have been able to isolate and characterize the microorganisms or even the enzymes involved in the transformation of these compounds or their derivatives. In studies involving 18O labeling as well as the use of cofactors and coenzymes, it was possible to prove that specific enzymes (e.g., mono- or dioxygenases) are involved in a particular degradation step. By using H2 18O, it could be shown that in certain transformation reactions, the oxygen was derived from water and that therefore these reactions might also occur under anaerobic conditions.  相似文献   

14.
15.
Substance P as well as many other neuropeptides are synthesized as glycine-extended precursors and converted to the biologically active C-terminal amides by posttranslational modification. The final step of posttranslational processing is catalyzed by peptidylglycine alpha-amidating monooxygenase (PAM). In a previous study, N-substituted homocysteine analogs were found to be potent inhibitors of PAM partially purified from conditioned medium of cultured rat medullary thyroid carcinoma CA-77 cells. These compounds, however, were only modest inhibitors of substance P production in cultured dorsal root ganglion cells, possibly because of poor cell penetration. Several ester derivatives of hydrocinnamoyl-phenylalanyl-homocysteine, one of the most potent PAM inhibitors, were prepared to increase the intracellular accessibility of these compounds. Hydrocinnamoyl-phenylalanyl-(S-benzoyl-homocysteine) benzyl ester was identified as the most potent compound, inhibiting substance P biosynthesis in dorsal root ganglion cells with an IC50 of 2 microM. Inhibition of PAM resulted in a concomitant increase in the glycine-extended substance p (substance P-Gly) precursor peptide. In the presence of 3 microM benzyl ester derivative, the intracellular substance P-Gly level was 2.4-fold higher while the substance P level was 2.1-fold lower than the corresponding peptides in control cells. These results suggest that PAM inhibition represents an effective method for suppression of substance P biosynthesis and, therefore, may have therapeutic utility in conditions associated with elevated substance P levels. Furthermore, PAM inhibition may also prove useful in decreasing other amidated peptides.  相似文献   

16.
The aromatic amine, 3,4-dichloroaniline (DCA) is an important intermediate in the chemical production of agricultural chemicals. A previous study had shown that nephrotoxicity was apparent 48 h after injection of 3,4-DCA. The purpose of this study was to examine the potential for 3,4-DCA to be toxic to the kidney, liver and urinary bladder 24 h after acute administration. Male Fischer 344 (F344) rats were injected (intraperitoneal (i.p.)) with 0.4, 0.8 or 1.0 mmol/kg 3,4-DCA hydrochloride (HCl) salt (2.5 ml/kg, 25% ethanol). Nephrotoxicity was apparent within 24 h in the 0.8 and 1.0 mmol/kg 3,4-DCA treated group and was characterized by elevated (P < 0.05) blood urea nitrogen (BUN) and kidney weight. Renal cortical slice accumulation ofp-aminohippurate (PAH) was also decreased in the 0.8 and 1.0 mmol/kg 3,4-DCA treated group relative to pair fed controls (PFC). Cellular changes were noted in the liver and bladder 24 h after 3,4-DCA administration. Plasma alanine transaminase (ALT) activity was elevated (P < 0.05) above PFC values 24 h after treatment with 0.8 or 1.0 mmol/kg indicating liver damage was apparent within 24 h. Morphological damage was apparent along the centrilobular region. Hematuria was observed in the 0.8 and 1.0 mmol/kg 3,4-DCA treated groups. Infiltration of erythrocytes and polymorphonuclear leukocytes was apparent within the urinary bladder upon examination by light microscopy. These results indicated that 3,4-DCA was toxic within 24 h and that the target tissues were the kidney, liver and urinary bladder. In vitro studies were conducted to compare the toxicity of two forms of 3,4-DCA, the free base and hydrochloride salt to determine whether chemical form contributes to renal cortical slice toxicity. Lactate dehydrogenase (LDH) release was elevated above control by 120 min exposure to 2 mM 3,4-DCA free base or hydrochloride salt. Pyruvate directed gluconeogenesis in renal slices was decreased relative to control by 0.5 mM 3,4-DCA free base and hydrochloride salt. The results from the in vitro studies indicates that the chemical form did not modify in vitro renal cortical slice toxicity.  相似文献   

17.
Several RGD peptidomimetics have been prepared, in a convergent way, from the common ortho-aminotyrosine template (O-substituted with an anchorage-arm or a methyl group, and alpha N-substituted with a fluorine tag for XPS analysis), and various omega-aminoacid derivatives. The most flexible compounds have shown a biological activity similar to that of the peptide reference (RGDS) in the platelet aggregation test. The compound 16a could be fitted (by modelisation) with DMP 728 and c(RGDfV), two cyclic peptides that are good ligands of integrins. The compound 16b has been covalently fixed on the surface of a poly(ethylene terephthalate) membrane used as support for mammalian cell cultivation.  相似文献   

18.
Phenol is a man-made as well as a naturally occurring aromatic compound and an important intermediate in the biodegradation of natural and industrial aromatic compounds. Whereas many microorganisms that are capable of aerobic phenol degradation have been isolated, only a few phenol-degrading anaerobic organisms have been described to date. In this study, three novel nitrate-reducing microorganisms that are capable of using phenol as a sole source of carbon were isolated and characterized. Phenol-degrading denitrifying pure cultures were obtained by enrichment culture from anaerobic sediments obtained from three different geographic locations, the East River in New York, N.Y., a Florida orange grove, and a rain forest in Costa Rica. The three strains were shown to be different from each other based on physiologic and metabolic properties. Even though analysis of membrane fatty acids did not result in identification of the organisms, the fatty acid profiles were found to be similar to those of Azoarcus species. Sequence analysis of 16S ribosomal DNA also indicated that the phenol-degrading isolates were closely related to members of the genus Azoarcus. The results of this study add three new members to the genus Azoarcus, which previously comprised only nitrogen-fixing species associated with plant roots and denitrifying toluene degraders.  相似文献   

19.
Photodegradation of naproxen and tiaprofenic acid in aqueous buffered solutions leads to decarboxylated products with ethyl, 1-hydroxyethyl and/or acetyl side chains. The photomixtures obtained in the presence of oxygen were clearly more toxic to cultured hepatocytes than those obtained under anaerobic conditions. This effect was more noticeable in the case of naproxen. Based on the composition of the oxygenated photomixtures and the relative toxicity of the different photoproducts, it is possible to account for most of the observed toxicity in the case of tiaprofenic acid but not in the case of naproxen. This is explained as a result of the presence of drug-derived peroxidic species in the photomixtures and their contribution to the observed toxicity. Peroxides were determined by the peroxidase-catalyzed oxidation of dichlorodihydrofluorescein to its fluorescent analog. The amount of peroxides present in naproxen photomixtures was much higher than in the case of tiaprofenic acid. A dose-dependent depletion of intracellular glutathione was observed when hepatocytes were incubated with peroxide-containing naproxen photomixtures. This effect was prevented by the addition of catalase or N-acetylcysteine to the culture medium.  相似文献   

20.
The influence of vitamin A-related compounds on hyperplasia and metaplasia induced by methylcholanthrene was studied in mouse prostate glands in organ culture. Methylcholanthrene was found to cause extensive hyperplasia and squamous metaplasia of the prostatic epithelium which persisted after withdrawal of the carcinogen. The retinoids included retinoic acid and 6 of its structural analogues synthesized in an attempt to enhance the anticarcinogenic action and reduce the toxicity of the parent compound. These where the cyclopentenyl analogus 7699, A2-retinoic acid, 13-cis-alpha-retinoic acid and 3 aromatic analogues. Administration of the compounds following the carcinogen reduced the extent and incidence of hyperplasia significantly and with the exception of one compound reversed the squamous metaplasia. Two of the aromatic analogues, one with a terminal ethylamide group (1430), and the other with a terminal ethylester group (9369), proved to be the most potent inhibitors, followed by compound 7699 and (9369), proved to be the most potent inhibitors, followed by compound 7699 and retinoic acid. A2-retinoic acid and 13-cis-alpha-retinoic acid showed the lowest activity. The inhibition of hyperplasia appeared to be mediated via a reduction of DNA synthesis. It seemed unrelated to either the biological growth-promoting activity of the compounds or their surface-active properties. It is tentatively suggested that vitamin A and its analogues may act as hormones.  相似文献   

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