Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.6.1 (sulfatase)
 3,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Urinary arylsulfatase A activity expressed as units/mg of urinary creatinine was significantly increased in bladder cancer patients, but not in patients with other genitourinary tract disorders, such as cystitis, urethritis and prostatic cancer, nor in patients with non-urological malignant diseases. The urinary enzyme activity was positively correlated with the stage of the bladder cancer, while post surgical follow-up revealed a marked decrease of the activity. Arylsulfatase A activity was also shown to be higher in malignant than in normal bladder tissue, demonstrating the activity to be a function of the grade of the tumor. Furthermore, the isoelectric point (pI 5.2-5.3) of the tissue enzyme in the bladder tumor coincided with that of the urine enzyme from the same cancer patients; the pI of the enzyme in urine from normal subjects was 4.7. These results suggest that most of the urinary arylsulfatase A in bladder cancer originates from tumor tissue.
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PMID:Arylsulfatase A activities in urine and tissues taken from bladder cancer patients. 615 61

Incubation of 2.5 microM benzo(a)pyrene (BaP) with C3H/10T 1/2 or CVP3SC6 (CVP) mouse fibroblasts for 48 hr resulted in the metabolism of 36 to 42% of the BaP to organic soluble derivatives, which cochromatographed with 7,8-trans-dihydroxy-7,8-dihydrobenzo(a)pyrene, 9,10-trans-dihydroxy-9,10-dihydrobenzo(a)pyrene, 3-hydroxybenzo(a)pyrene, and 9-hydroxybenzo(a)pyrene, or to water-soluble derivatives. The formation of both organic and water-soluble metabolites during the 48-hr period increased proportionally with time, except in the case of BaP phenols, which increased initially but then remained the same or decreased. The distribution of organic soluble metabolites in the extracellular culture medium consisted primarily of BaP diols and was significantly different from that found inside the cells. The intracellular profile of organic soluble metabolites produced by both cell lines consisted predominantly of BaP phenolic derivatives and was qualitatively similar to the spectrum of metabolites produced by the incubation of BaP with C3H/10T 1/2 or CVP cell microsomes. The nature of the BaP water-soluble derivatives produced by the C3H/10T 1/2 and CVP cell lines was investigated by hydrolysis of culture medium with beta-glucuronidase and arylsulfatase. Although sulfation was not a major conjugation pathway for BaP in these cells, glucuronidation of BaP phenols was found to account for 30% of the total water-soluble derivatives. The similarity in the kinetics and qualitative nature of the metabolism of BaP by C3H/10T 1/2 and CVP cells indicates that both cell lines are equally capable of biosynthesizing the proximal carcinogen, 7,8-trans-dihydroxy-7,8-dihydrobenzo(a)pyrene. Analysis of the water-soluble metabolites produced by these cells suggests further that the nonresponsiveness of the CVP cells to BaP-induced transformation cannot be accounted for on the basis of an increased detoxication of 7,8-trans-dihydroxy-7,8-dihydrobenzo(a)pyrene.
Cancer Res 1982 Jul
PMID:Metabolic activation of benzo(a)pyrene by transformable and nontransformable C3H mouse fibroblasts in culture. 628 46

The possibility that pancreatic secretory abnormalities might precede the appearance of pancreatic neoplasms and thus provide clues to early detection of this malignancy has been investigated in an animal model. Syrian golden hamsters were treated with bis-(2-oxopropyl)-N-nitrosamine on two successive weeks (2 mg/100 g body weight/week). Pancreatic secretions from treated and untreated control animals were studied at approximately monthly intervals. The animals were anesthetized, their pancreatic ducts cannulated, and basal pancreatic juice collected for 30 min. Pancreatic secretion was then stimulated by sequential intravenous injection of secretin (50 ng/100 g) and C-terminal octapeptide of cholecystokinin (4 ng/100 g) 1 hr later. Four consecutive 15-min collections of fluid were made following secretin stimulation and four additional collections after CCK administration. Each collection was examined for volume, total protein, trypsin, chymotrypsin, elastase, arylsulfatase, beta-D-glucuronidase, alpha-D-glucosidase, and leucine naphthylamidase. In addition two trypsinogen variants present in pancreatic secretions were determined. The pancreas and other organs were removed and examined histologically at the end of each experiment. Cytological atypia appeared 3 months, ductal hyperplasia 4 months, and pancreatic neoplasms 6 months after the last injection of carcinogen. Striking decreases in flow rate and output of trypsin and chymotrypsin were observed several months prior to the appearance of histologically recognizable pancreatic tumors. By contrast, output of beta-D-glucuronidase and alpha-D-glucosidase in pancreatic juice increased markedly in the last 2 months preceding the emergence of neoplasms. The diagnostic significance of these premalignant abnormalities is illustrated most dramatically in the form of ratios of lysosomal to digestive enzymes, such as beta-D-glucuronidase-trypsin or alpha-D-glucosidase-chymotrypsin. Highly significant increases in these ratios were observed consistently, not only in hamsters with pancreatic neoplasms, but also in animals with preneoplastic lesions (ductular hyperplasia) which preceded malignancies by about 2 months.
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PMID:Pancreatic secretory abnormalities precede appearance of tumors of the pancreas in hamsters treated with bis-(2-oxopropyl)-N-nitrosamine. 630 6

The activity of the two membrane-bound sulfatases, estrone and dehydroepiandrosterone sulfatases, are reported in human breast carcinoma tissues. In 21 tested tumors (12 from post-menopausal women and 9 from nonmenopausal women), the two sulfatases were consistently present. The apparent Km values for estrone and dehydroepiandrosterone sulfatases were, respectively, 6.8 and 14.9 microM. In terms of maximal velocity, the sulfatase activities are not correlated to the estrogen or progesterone receptor status of the tumors or to the hormonal status of the donors. It may be concluded that these two activities are not hormone dependent. Estrone sulfate, the substrate of estrone sulfatase, has been measured in plasma of postmenopausal women. The mean levels (nmol/liter) of plasma estrone sulfate were compared in post-menopausal women with (n = 51) or without (n = 39) breast cancer. For the first age group (48 to 55 years old), no statistically significant difference in these levels was observed [1.91 +/- 1.06 versus 1.50 +/- 1.04 (mean +/- t0.95 (Formula: see text) S.E.)]. For the two other age groups (56 to 65 and 66 to 80 years of age), the differences were statistically significant [1.46 +/- 0.43 versus 0.77 +/- 0.21 (p less than 0.02) and 1.77 +/- 0.53 versus 0.81 +/- 0.22 (p less than 0.01)]. The usefulness of plasma estrone 3-sulfate levels as an indicator of the real estrogen status of postmenopausal women is discussed.
Cancer Res 1984 Feb
PMID:Estrone and dehydroepiandrosterone sulfatase activities and plasma estrone sulfate levels in human breast carcinoma. 658 63

Glycosidases were determined in the supernatant from normal, benign, premalignant, and cancerous human tissue. The total enzyme activities of alpha-fucosidase, hexosaminidase, beta-galactosidase, and acid phosphatase in both malignant tumors and tissues with premalignant lesions were significantly greater than those in normal tissues, whereas a very low enzyme activity alteration in benign lesions was observed. The least specific enzyme alteration was aryl sulfatase, which was elevated in only 58% of the tissues with malignancies and in 19% of the tissues with benign lesions. Nearly 90% of tissues with premalignant lesions had simultaneously elevated levels of two or more enzymes whereas only 5% of the control tissues had simultaneously elevated alpha-fucosidase, hexosaminidase, and acid phosphatase activity. Present results indicate that acid glycosidases have high activity in both premalignant and malignant human tissues.
Cancer Detect Prev 1984
PMID:Alterations of glycosidases in benign, premalignant and malignant human lesions. 670 3

The plasma pharmacokinetics of the antineoplastic anthracycline antibiotic aclacinomycin A (Acm) and its metabolites were studied in 12 patients treated with 60-120 mg/m2 during a phase I clinical trial. Total plasma drug fluorescence initially declined very rapidly, but from 2 to 24 h after injection, fluorescence rose progressively to intensities greater than those measured 1 min after Acm injection. Plasma total drug fluorescence slowly declined from 24 to 72 hours after Acm administration. These events reflected the rapid disappearance of Acm and the subsequent appearance of two highly fluorescent metabolites. One metabolite co-chromatographed with and had a fluorescence spectrum identical to known metabolite F1 (bisanhydroaklavinone). The other metabolite did not co-chromatograph with any previously described Acm metabolite. This metabolite had a fluorescence spectrum unlike any previously described Acm metabolite and was not altered by treatment for 60 min with 0.2 N HCl at 100 degrees C or by treatment for 24 h at 37 degrees C with bacterial beta-glucuronidase or limpet aryl sulfatase.
Cancer Chemother Pharmacol 1982
PMID:Plasma kinetics of aclacinomycin A and its major metabolites in man. 695 15

Phenacetin was mutagenic in Salmonella typhimurium TA100 in plate assays when liver fractions from Aroclor-treated hamsters, but not rats, were used. Its known or putative metabolites were synthesized; of these, N-hydroxyphenacetin and N-acetoxyphenacetin were found to be mutagenic in liquid and plate assays, both requiring activation by liver fractions from Aroclor-treated hamsters. 2-Hydroxyphenacetin and 2-acetoxyphenacetin were nonmutagenic. N-Hydroxyphenetidine (the deacetylated metabolite of phenacetin) and p-nitrosophenetole were the only products that were found to be mutagenic per se when assayed under N2 in either Salmonella TA100 and TA100 NR (nitroreductase-deficient) strains. Phenacetin was administered to male BDVI rats and Syrian golden hamsters, and its urinary metabolites were deconjugated with beta-glucuronidase:arylsulfatase. After reactivation by hamsters liver fractions, mutagenicity was demonstrated in S. typhimurium TA100 with urine from phenacetin-treated hamsters, but not with that from rats. After treatment with deconjugating enzymes, N-hydroxyphenacetin was isolated from hamster urine by high-performance liquid chromatography and identified by mass spectral analysis. The data support the conclusions that (a) N-hydroxyphenacetin is a proximate mutagenic metabolite of phenacetin which, after N-deacylation, is responsible for the mutagenicity observed in vitro and in the urine of hamsters and (b) the higher yield of N-hydroxyphenacetin that is formed in the liver of hamsters as compared to rats explains the pronounced species-specific activation of phenacetin into bacterial mutagens.
Cancer Res 1982 Aug
PMID:Species-specific activation of phenacetin into bacterial mutagens by hamster liver enzymes and identification of N-hydroxyphenacetin O-glucuronide as a promutagen in the urine. 704 20

The activities of arylsulfatases A and B were determined in human primary and secondary tumor tissues (total, 53 cases) of various histological types. Significantly higher activities of these sulfatases were found in almost all the primary lung carcinomas as compared to their corresponding uninvolved tissues. No significant correlation was demonstrated between the enzyme activities and histological figures (stroma amounts, etc.). Lung adenocarcinoma and squamous cell carcinoma showed the presence of an additional arylsulfatase component (B1) which was not detected in normal human lung. The tumor arylsulfatase B1 had an isoelectric point (pI) of 6.7 and was clearly distinguished from arylsulfatase A (pI 4.9) and arylsulfatase B (pI 9.1 to 9.2) in normal lung and lung tumor. The tumor B1 enzyme was demonstrated to be most probably an isoenzyme of arylsulfatase B, since this unusual enzyme was indistinguishable from arylsulfatase B in terms of Ag+ inhibition; its kinetic parameters of Km for p-nitrocatechol sulfate, which was 2.9 mM with B1; optimum pH of 6.3 for B1; heat stability; and substrate specificity for three synthetic and two physiological substrates.
Cancer Res 1980 Oct
PMID:Elevated activities and properties of arylsulfatases A and B and B-variant in human lung tumors. 743 63

The evaluation of estrogens (estrone, estradiol, and their sulfates) in the breast tissue of post-menopausal patients with breast cancer indicates high levels, particularly of estrone sulfate (E1S) which is 15-25 times higher than in the plasma. Breast cancer tissue contains the enzymes necessary for local synthesis of estradiol and it was demonstrated that, despite the presence of the sulfatase and its messenger in hormone-dependent and hormone-independent breast cancer cells, this enzyme operates particularly in hormone-dependent cells. Different progestins: Nomegestrol acetate, Promegestone, progesterone, as well as Danazol, can block the conversion of E1S to E2 very strongly in hormone-dependent breast cancer cells. The last step in the formation of estradiol is the conversion of E1 to this estrogen by the action of 17 beta-hydroxysteroid dehydrogenase. This activity is preferentially in the reductive direction (formation of E2) in hormone-dependent cells, but oxidative (E2-->E1) in hormone-independent cells. Using intact hormone-dependent cells it was observed that Nomegestrol acetate can block the conversion of E1 to E2. It is concluded, firstly, that in addition to ER mutants other factors are involved in the transformation of hormone-dependent breast cancer to hormone-independent, this concerns the enzymatic activity in the formation of E2; it is suggested that stimulatory or repressive factor(s) involved in the enzyme activity are implicated as the cancer evolves to hormone-independence; secondly, different drugs can block the conversion of E1S to E2. Clinical trials of these "anti-enzyme" substances in breast cancer patients could be the next step to investigate new therapeutic possibilities for this disease.
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PMID:Estrone sulfate-sulfatase and 17 beta-hydroxysteroid dehydrogenase activities: a hypothesis for their role in the evolution of human breast cancer from hormone-dependence to hormone-independence. 762 88

Tea has been shown to inhibit chemically induced tumorigenesis in many animal models, but the effects of tea consumption on human carcinogenesis are not conclusive. In order to develop biomarkers for tea consumption, we developed methods for the analysis of tea polyphenols in human plasma and urine samples using HPLC with the coulochem electrode array detection system. (-)-Epigallocatechin-3-gallate (EGCG), (-)-epigallocatechin (EGC), (-)-epicatechin-3-gallate (ECG), and (-)-epicatechin (EC) are the major polyphenols in green tea. Most of the tea polyphenols were in their conjugated forms in the plasma and urine. The samples were incubated with a mixture of beta-glucuronidase and sulfatase to generate the free form of tea polyphenols. After extraction into ethyl acetate and separation by reversed-phase chromatography, EGCG, EGC, and EC were identified on the basis of their retention times and electrochemical characteristics. Due to the high selectivity of the detection mode, interference was minimized. Good quantitative relationships were established for a large concentration range of tea polyphenols. The limits of detection for EGCG, EGC, ECG, and EC were from 0.5 to 1.5 ng/ml of plasma or urine sample. After ingestion of 1.2 g of decaffeinated green tea in warm water, the plasma samples collected at 1 h from 4 human volunteers contained 46-268 ng/ml of EGCG, 82-206 ng/ml of EGC, and 48-80 ng/ml of EC. ECG was not detected in plasma samples. The maximum urinary excretion of EGC and EC occurred at 3-6 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Cancer Epidemiol Biomarkers Prev 1995 Jun
PMID:Analysis of plasma and urinary tea polyphenols in human subjects. 765 36


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