[20] 4-Nitrophenol UDPglucuronyltransferase (rat liver)

Burchell, Brian; Weatherill, Philip J.

doi:10.1016/s0076-6879(81)77022-8

Cited by 84 publications

(34 citation statements)

References 13 publications

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“…p-Nitrophenol UGT activity of the microsomal preparations was measured using the method of Burchell and Weatherill. (28) In brief, the same volume of microsomal sample solution (2.0 mg/mL), 1.5 mM p-nitrophenol dissolved in a UGT reaction buffer (75 mM Tris-HCl [pH 8.0] and 15 mM MgCl 2 ) and 6.0 mM UDP-glucuronic acid dissolved in UGT reaction buffer were incubated at 37°C for 10 min. The reaction was terminated by incubation in boiled water for 2 min, followed by mixing with 0.1 M KOH and cooling on ice for 30 min.…”

Section: Methodsmentioning

confidence: 99%

Increased susceptibility to hepatocarcinogenicity of Nrf2‐deficient mice exposed to 2‐amino‐3‐methylimidazo[4,5‐f]quinoline

Kitamura¹,

Umemura²,

Kanki³

et al. 2006

Cancer Science

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To elucidate the roles of the transcription factor NF-E2-related factor (Nrf2) in hepatocarcinogenesis induced by 2-amino-3-methylimidazo[4,5-f ]quinoline (IQ), a mutagenic and carcinogenic heterocyclic amine, Nrf2-deficient mice were treated with 300 p.p.m. IQ in their diet for 1, 4 or 52 weeks. In the long-term experiment, the multiplicity and incidence of liver tumors in male and female IQtreated Nrf2 deficient (-/-) mice were significantly higher than those in their counterpart wild-type (+/+) mice exposed to IQ. In the short-term experiment, although IQ exposure to Nrf2(+/+) mice of both sexes did not modify UDP-glucuronosyltransferase values, glutathione S-transferase values were significantly increased due to IQ treatment, in contrast to no alteration in male and female Nrf2(-/-) mice. Levels of oxidative stress markers such as 8-hydroxydeoxyguanosine and thiobarbituric acid reactive substances in the livers of all treated mice were not changed by IQ treatment. IQ-specific DNA adduct levels were elevated only in female Nrf2(-/-) mice, although the increase was not significant. IQ treatment caused an increase in proliferating cell nuclear antigen labeling indices only in male Nrf2(-/-) mice. The present data clearly show that Nrf2(-/-) mice of both sexes are susceptible to IQ hepatocarcinogenicity, which might result from IQ accumulation due to failure of metabolizing enzyme induction. In addition, inconsistent results concerning IQ-specific adducts and proliferating cell nuclear antigen labeling indices in male and female Nrf2(-/ (1) and also in cigarette smoke condensate (2) . IQ is carcinogenic to the liver, colon, small intestine, Zymbal's gland, clitoral gland and skin in F344 rats, (3) to the liver, forestomach and lung in CDF 1 mice, (4) and to the liver in B6C3F 1 mice (5) in long-term experiments. Recently, we have found that rat lung is also a target of IQ carcinogenicity.-(6) Its carcinogenesis is considered to involve mainly IQ bioactivation, that is phase I hepatic CYP1A1/2-mediated N-hydroxylation followed by phase II (mainly N-acetyltransferase and sulfotransferase) esterification of N-hydroxylamines to reactive ester derivatives that bind to DNA covalently. (7,8) In addition, it was suggested recently that oxidative stress may also participate in HCA carcinogenesis, based on the findings that induction of preneoplastic or neoplastic lesions following HCA exposure was significantly inhibited when given simultaneously with antioxidants in rats, (9,10) and that superoxide anion radicals were generated during metabolism of HCA by NADPH/cytochrome P-450 reductase in vitro using a spin-trapping method.(11) We have demonstrated enhancement of IQ-induced colon tumor development due to cotreatment with NaNO 2 and the participation of oxidative stress such as oxidative DNA damage and lipid peroxidation in this phenomenon. However, IQ-induced liver tumors were only slightly increased by the addition of NaNO 2 , the relation to oxidative stress being equivocal.(12) Thus, IQ causes carcinogenesis in a b...

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Section: Methodsmentioning

confidence: 99%

Increased susceptibility to hepatocarcinogenicity of Nrf2‐deficient mice exposed to 2‐amino‐3‐methylimidazo[4,5‐f]quinoline

Kitamura¹,

Umemura²,

Kanki³

et al. 2006

Cancer Science

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“…Multidrug-resistant cells often possess defects in drug accumulation (2) and frequently contain increased levels of membrane glycoproteins of high molecular mass (130-170 kDa) (3)(4)(5) and cytosolic proteins of low molecular mass (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) (6,7). However, the precise mechanisms whereby cells can develop simultaneous resistance to multiple agents that differ markedly in both structures and mechanisms of action are as yet unclear.…”

mentioning

confidence: 99%

“…GSHTase activity was assayed using dichloronitrobenzene as the substrate (19), glutathione peroxidase was assayed using H202 or cumene hydroperoxide (20), and UDP-glucuronyltransferase (21) was assayed using 4-nitrophenol according to assays previously described. Aryl hydrocarbon hydroxylase (AHHase) activity was measured using a fluorometric assay (22), and sulfotransferase activities (I/II and III/IV) were measured as described previously (23).…”

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confidence: 99%

Similar biochemical changes associated with multidrug resistance in human breast cancer cells and carcinogen-induced resistance to xenobiotics in rats.

Cowan

Batist

Tulpule

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

223

130

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MCF7 human breast cancer cells selected for resistance to doxorubicin (adriamycin; DoxR) have developed the phenotype of multidrug resistance. Multidrug resistance in DoxR MCF7 cells (called AdrR MCF7 cell line in previous publications) is associated with biochemical changes similar to those induced by carcinogens in rat hyperplastic liver nodules (HNs) and associated with resistance to xenobiotics in that system. In HNs and DoxR cells, exposure to a single agent results in the selection of cells that are cross-resistant to a wide variety of structurally dissimilar toxic agents. Resistance in both systems is associated with decreases in intracellular accumulation of toxins and changes in phase I (decreased cytochrome P1-450) and phase H (increased glutathione transferase and glucuronyltransferase) drug-metabolizing activities. In HNs and DoxR cells, resistance is associated with the induction of relatively stable levels of an immunologically related anionic glutathione transferase isozyme (EC 2.5.1.18). The rmding of similar biochemical changes associated with the development of resistance to various xenobiotics in HNs and to many naturally occurring antineoplastic agents and at least one carcinogen (benzo[a]pyrene) in DoxR MCF7 cells suggests that the mechanisms of resistance in these two models may be similar.

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“…High throughput assays were developed and were based on spectrophotometric loss of absorbance of the aglycone substrate upon glucuronidation [30]. Maximal absorbance for pnitrophenol and a-naphthol was 402 nm and 332 nm, respectively.…”

Section: Spectrophotometric Assaymentioning

confidence: 99%

Pharmacogenetic Factors Contributing to Variation in Response to Tamoxifen at Raloxifene

Raftogianis¹

2004

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[20] 4-Nitrophenol UDPglucuronyltransferase (rat liver)

Cited by 84 publications

References 13 publications

Increased susceptibility to hepatocarcinogenicity of Nrf2‐deficient mice exposed to 2‐amino‐3‐methylimidazo[4,5‐f]quinoline

Increased susceptibility to hepatocarcinogenicity of Nrf2‐deficient mice exposed to 2‐amino‐3‐methylimidazo[4,5‐f]quinoline

Similar biochemical changes associated with multidrug resistance in human breast cancer cells and carcinogen-induced resistance to xenobiotics in rats.

Pharmacogenetic Factors Contributing to Variation in Response to Tamoxifen at Raloxifene

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