Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary aromatic amines have been identified epidemiologically as human carcinogens. It has been suggested that the target organ affected by aromatic amines is dependent on the rate of metabolic activation. Epidemiological studies have shown an association between low acetyl transferase activity and bladder cancer risk. On this basis, our working hypothesis was that the slow acetylators could follow in a higher extent the metabolic pathway independent of N-acetylation, leading to the excretion of conjugates of electrophyles with glucuronic acid. The instability of these glucuronides could be responsible for the association between arylamine-induced bladder cancer and slow acetylator phenotype. A total of 153 individuals were included in this study: 70 exposed to arylamines (working in textile industry) and 83 nonexposed. The following parameters were determined in urine: mutagenic index in the absence of metabolic activation, S9; mutagenic index in the presence of S9; and the mutagenic index after incubation of the urine with beta-glucuronidase. All individuals were phenotyped according to their capacity of N-acetylation by using isoniazid as drug test. The results show that the mutagenic index after incubation of the urine with beta-glucuronidase is statistically higher in exposed subjects when compared with nonexposed individuals (P less than 0.001), this parameter being statistically higher among exposed subjects who were slow acetylators than among rapid metabolizers, independent of the fact that they were smokers or nonsmokers. There were no significant differences between groups for the mutagenicity in urine not incubated with beta-glucuronidase.
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PMID:Urinary mutagenicity and N-acetylation phenotype in textile industry workers exposed to arylamines. 151 45

To treat superficial bladder cancer or invasive bladder cancer presenting as a solitary tumor, conservative therapy such as transurethral resection of bladder tumor or partial cystectomy has long been carried out. We studied the effect of 1-hexylcarbamoyl-5-fluorouracil (HCFU), and the effects of the combination of HCFU and 2.5-di-O-acetyl-D-glucaro-(1-4)(6-3) dilactone (SLA) which is an anti-beta-glucuronidase agent, for preventive therapy. In the patients treated with HCFU, the recurrence rate was 3.6% and 26.6% one year and two years, respectively, after conservative operation. In the patients treated with both SLA and HCFU, the recurrence rate was lower than in those treated with HCFU one year or more after conservative operation, and a long-term preventive effect was expected for nondrinkers.
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PMID:[Study of preventive effect of 1-hexylcarbamoyl-5-fluorouracil (HCFU) or combination of HCFU and 2.5-di-O-acetyl-D-glucaro (1-4) (6-3) dilactone (SLA) after preservative operation against bladder cancer]. 154 64

The enzymatic profile of urine and plasma in field cases of bovine bladder cancer was studied. Urinary lactate dehydrogenase activity was significantly altered along with the isoenzyme pattern. Activity of alkaline phosphatase and beta-glucuronidase was decreased in the affected animals. No significant changes were observed in acid phosphatase, or arylsulphatase A and B activity. In plasma, lactate dehydrogenase activity was elevated without any change in the isoenzyme pattern. No significant changes were observed in the other plasma enzymes studied or in the sialic acid concentration.
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PMID:The enzymatic profile of urine and plasma in bovine urinary bladder cancer (enzootic bovine haematuria). 180 21

The relationship between parasite infestation and chemical mutagen metabolism was investigated in this study. Schistosoma hematobium, long associated with increased incidence of bladder cancer in humans, was chosen as a model parasite. Urine samples, serum samples, and liver tissue extracts (S-9) from infested and control hamsters were used with the Ames Salmonella/microsome test to follow 3,3'-dichlorobenzidine (DCB), aflatoxin B1 (AFB1), and 2-acetylaminofluorene (AAF) mutagenicity. Liver S-9 preparations from infested and control hamsters showed little difference in activation potential for DCB and AFB1. Aroclor 1254-induced rat liver S-9, however, was remarkably efficient at reducing the mutagenicity of DCB. This process was reversible by beta-glucuronidase (BG). Studies on infested and control hamsters indicated increased BG activity in serum and urine. Urine concentrates (UC) from infested and control animals were not mutagenic by themselves, but did enhance the mutagenicity of AAF and DCB in the presence of S-9 and BG. Urine concentrates from infested animals showed greater enhancement of DCB mutagenicity than did UC from control animals. These data suggest that increased BG and unknown urinary factors in infested hamsters play a role in altering chemical mutagen activity.
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PMID:Modified mutagen metabolism in Schistosoma hematobium-infested organisms. 392 19

Studies showing that bladder cancer patients have unusually high levels of urinary beta-glucuronidase and arylsulfatases A and B led to the suggestion that these urinary enzymes may participate in bladder cancer etiology. An alternative explanation of the high levels of these urinary enzymes in bladder cancer patients is that the disease itself causes the elevation. Since the levels of these enzymes are genetically determined, measuring these enzymes in healthy identical twins of bladder cancer patients can test whether high enzyme levels occurred prior to bladder cancer. Five healthy identical cotwins of bladder cancer patients, together with matched controls, were measured for urinary beta-glucuronidase, arylsulfatases A and B, and two other lysosomal enzymes as controls, alpha- and beta-galactosidases. The mean levels of all five enzymes were not very different in the cotwins and controls, suggesting that high levels of urinary enzymes observed in bladder cancer patients are a consequence of disease rather than occurring prior to disease and contributing to its etiology.
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PMID:Urinary glucuronidase and arylsulfatases in identical twins of bladder cancer patients. 614 1

The histochemical enzyme activity of alkaline phosphatase, nonspecific esterase, 5-nucleotidase, beta-glucuronidase, glucose-6-phosphatase, succinate dehydrogenase, and glucose-6-phosphate dehydrogenase in human bladder cancer was investigated. Tumors of 84 patients, classified into grades I-III according to the WHO classification, were compared with 12 normal and 16 inflamed bladder epithelia. As a rule, loss of alkaline phosphatase activity and a decrease of nonspecific esterase activity was found in most of these tumors. The activity of beta-glucuronidase was decreased and compared with normal tissue, also the activity of 5-nucleotidase. The succinate dehydrogenase activity in tumor tissue was frequently increased, whereas glucose-6-phosphate dehydrogenase did not show any significant reaction.
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PMID:[Histochemical investigations on human bladder cancer (author's transl)]. 626 65

It has been suggested that high levels of urinary beta-glucuronidase may increase an individual's risk of bladder cancer by releasing free carcinogens from their inactive glucuronide conjugates in the bladder. The hypothesis derives in part from the high levels of urinary beta-glucuronidase observed in bladder cancer patients. Because most of the individual variation in levels of urinary beta-glucuronidase and other lysosomal enzymes in the normal population is genetically determined, we would expect that, if high glucuronidase levels were a predisposing factor in the disease, bladder cancer patients would transmit this trait to their progeny. We have tested this hypothesis and find that levels of urinary beta-glucuronidase and three other lysosomal enzymes, alpha-galactosidase, beta-galactosidase, and beta-hexosaminidase, are not significantly elevated in 34 progeny of bladder cancer patients compared to 34 matched controls. Additionally, 15 bladder cancer patients judged to be disease free for a median time of 5 years did not have elevated levels of urinary beta-glucuronidase when compared to a normal population of 125 individuals. Thus, the high levels of glucuronidase observed in bladder cancer patients are most likely a consequence of disease rather than a cause.
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PMID:Role of urinary beta-glucuronidase in human bladder cancer. 633 54

Several epidemiological, clinical and experimental studies have been carried out to determine whether there is an aetiological role for schistosomiasis in the multi-stage process of bladder carcinogenesis. Lines of evidence supporting the association between bladder cancer and schistosomiasis include indications from the geographical correlation between the two conditions, the distinctive patterns of gender and age at diagnosis, the clinicopathological identity of schistosome-associated bladder cancer and the extensive experimental evidence in infected laboratory animals. Although the causative role of schistosomiasis is now accepted, various associated factors have been proposed in the induction of this particular type of cancer. While all may contribute to the carcinogenic process taking place in the infected bladder, none of these has yet been confirmed. Most attention has been directed at theories proposing possible roles for urinary chemical carcinogens, particularly tryptophan metabolites, N-nitroso compounds and of beta-glucuronidase, as factors that are primarily involved in the initiation of bladder carcinogenesis in areas endemic for schistosomiasis.
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PMID:Role of schistosomiasis in human bladder cancer: evidence of association, aetiological factors, and basic mechanisms of carcinogenesis. 772 97

Human urine is known to contain substances that strongly inhibit bacterial mutagenicity of aromatic and heterocyclic amines in vitro. The biological relevance of these anti-mutagens was examined by comparing levels of tobacco-related DNA adducts in exfoliated urothelial cells from smokers with the anti-mutagenic activity in corresponding 24-h urine samples. An inverse relationship was found between the inhibition of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-mutagenicity by urine extracts in vitro and two DNA adduct measurements: the level of the putatively identified N-(deoxyguanosine-8-yl)-4-aminobiphenyl adduct and the total level of all tobacco-smoke-related carcinogen adducts including those probably derived from PhIP. Urinary anti-mutagenicity in vitro appears thus to be a good indicator of the anti-genotoxicity exerted by substances excreted in urine, that protect the bladder mucosal cells (and possibly other cells) against DNA damage. These substances appear to be dietary phenolics and/or their metabolites because (i) the anti-mutagenic activity of urine extracts (n = 18) was linearly related to their content in phenolics; (ii) the concentration ranges of these substances in urine extracts were similar to those of various plant phenols (quercetin, isorhamnetin and naringenin) for which an inhibitory effect on the liver S9-mediated mutagenicity of PhIP was obtained; (iii) treatment of urines with beta-glucuronidase and arylsulfatase enhanced both anti-mutagenicity and the levels of phenolics in urinary extracts; (iv) urinary extracts inhibited noncompetitively the liver S9-mediated mutagenicity of PhIP as did quercetin, used as a model phenolics. Several structural features of the flavonoids were identified as necessary for the inhibition of PhIP and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxiline mutagenicity. Fractionation by reverse-phase HPLC and subsequent analysis of two urinary extracts, showed the presence of several anti-mutagenic substances and phenolics; more lipophilic phenolics displayed the highest specific inhibitory activity. This suggests that enzymatic conversion of dietary flavonoids into their more lipophilic and anti-mutagenic O-methylcatechol derivatives, as noted for quercetin, may occur in vivo in man. Onion, lettuce, apples and red wine are important sources of dietary flavonoids which are probably responsible for the anti-mutagenicity associated with foods and beverages. After HPLC fractionation of urinary extracts, the distribution profile of anti-mutagenic activity corresponded roughly to that of onion and wine extract combined. Our study strongly suggests that smokers ingesting dietary phenolics, probably flavonoids, are partially protected against the harmful effects by tobacco carcinogens within their bladder mucosal cells. This protective effect of dietary phenolics against the cancer of the bladder (and possibly other sites) should be verified and explored as a part of a chemoprevention strategy.
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PMID:Dietary phenolics as anti-mutagens and inhibitors of tobacco-related DNA adduction in the urothelium of smokers. 889 88

The two major causes of bladder cancer have been recognised to be cigarette smoke and occupational exposure to arylamines. These compounds are present both in tobacco smoke and in the dyes used in textile production. Aromatic amines suffer oxidative metabolism via P450 cytochrome CYP1A2, and detoxification by the polymorphic NAT2. The aim of the present work was to assess the association between occupational-derived exposure to mutagens and CYP1A2 or NAT2 activity. This cross-sectional study included 117 textile workers exposed to dyes and 117 healthy controls. The urinary mutagenicity was determined in 24 h urine using TA98 Salmonella typhimurium strain with microsomal activation S9 (MIS9) or incubation with beta-glucuronidase (MIbeta). Urinary caffeine metabolite ratios: AFMU+1X+1U/17U, and AFMU/AFMU+1X+1U were calculated to assess CYP1A2 and NAT2 activities, respectively. The results show that workers present a strikingly higher urine mutagenicity than controls (p<0.0001), despite the implementation of the new restrictive norms forbidding the industrial use of the most carcinogenic arylamines. Neither NAT2 nor CYP1A2 activity had any effect on the markers of internal exposure to mutagens, since no significant differences were observed when the urinary mutagenicity of slow and fast acetylators (p>0.05) was compared, and the urinary mutagenicity was not significantly associated with the CYP1A2 activity marker (r=0.04 and r=-0.01 for MIS9 and MIbeta, respectively). This study clearly indicates the need for further protective policies to minimise exposure to the lowest feasible limit in order to avoid unnecessary risks.
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PMID:Urinary mutagenicity, CYP1A2 and NAT2 activity in textile industry workers. 1561 66


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