CYP4B1 Is a Possible Risk Factor for Bladder Cancer in Humans

Imaoka, Shingi; Yoneda, Yukio; Sugimoto, Toshikado; Hiroi, Toyoko; Yamamoto, Keisuke; Nakatani, Tatsuya; Funae, Yoshihiko

doi:10.1006/bbrc.2000.3740

Cited by 64 publications

(43 citation statements)

References 16 publications

(25 reference statements)

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“…Analysis of additional cytochrome P450 isoforms that are discussed as being relevant in the metabolism of aromatic amines in bladder epithelial cells, namely CYP4B1 and CYP1B1 (Imaoka et al 2000;Carnell et al 2004), did not indicate signiWcant expression changes after incubation with B[a]P, 4-ABP or combinations of both (data not shown). The same was true for several transcripts related to DNA repair genes as Xeroderma pigmentosum group A protein (XPA), DNA helicase XPB (ERCC3), Xeroderma pigmentosum complementation group C and D (XPC, XPD), incision speciWc nuclease ERCC1 and X-ray repair cross-complementing group 1 (XRCC1) (Wood et al 2001, Sanyal et al 2004) (results not shown).…”

Section: Resultsmentioning

confidence: 96%

Synergism of aromatic amines and benzo[a]pyrene in induction of Ah receptor-dependent genes

et al. 2008

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Aromatic amines have been shown to cause bladder cancer. However, epithelial cells of the urinary bladder, cells of origin of bladder cancer, may be exposed to numerous substances besides aromatic amines. In the present study, we analysed possible interactions between the aromatic amines 4-aminobiphenyl (4-ABP) as well as 2-naphthylamine (2-NA) and the polycyclic aromatic hydrocarbon benzo[a]pyrene (B[a]P). For this purpose we incubated primary porcine urinary bladder epithelial cells (PUBEC) with concentrations of 1 to 50 M 4-ABP with and without coexposure to B[a]P. As expected B[a]P increased mRNA expression of cytochrome P450 1A1 (CYP1A1), whereas 4-ABP had no eVect. However, when co-exposed 4-ABP enhanced the induction of CYP1A1 by B[a]P. This result was conWrmed by Western blot analysis of CYP1A1 protein expression. A similar eVect as for CYP1A1 was also observed for cyclooxygenase-2 (COX-2) and UDP-glucuronosyltransferase 1 (UGT1). Next, we studied co-exposures of 2-NA and B[a]P. Similar as for 4-ABP also 2-NA enhanced B[a]P-mediated induction of CYP1A1. Our results demonstrate that some aromatic amines may enhance the inXuence of B[a]P on Ah receptor-dependent genes.

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Section: Resultsmentioning

confidence: 96%

Synergism of aromatic amines and benzo[a]pyrene in induction of Ah receptor-dependent genes

et al. 2008

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“…[15][16][17] It has been suggested that the induction levels show a correlation between enzyme activities or protein levels and mRNA levels after exposure to inducers. 18,19) One possible exception is the induction of CYP2E1 by ethanol and isoniazid, which is thought to result either from protein stabilization 20) or increased protein translation. 21) Therefore we considered that rapid estimation should be possible by evaluating the changes in the mRNA levels of target enzymes and transporters and then evaluating the changes in corresponding protein and activity levels.…”

Section: Fig 2 Time Course and Ešects On Levels Of Mrna Expression mentioning

confidence: 99%

Evaluation of Gene Induction of Drug-Metabolizing Enzymes and Transporters in Primary Culture of Human Hepatocytes Using High-Sensitivity Real-Time Reverse Transcription PCR

et al. 2002

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In the present study, the induction of drug-metabolizing enzymes and transporters was evaluated by analyzing mRNA expression in human hepatocytes after exposure to various compounds. The compounds tested included typical enzyme inducers, rifampicin and omeprazole, and controls. All experiments were performed in the presence of 0.1％ DMSO. Analysis was performed by the real-time reverse-transcription polymerase chain reaction method (RT PCR) in the presence of TaqMan probes using an ABI PRISM 7700 Sequence Detector system. A new analytic method to quantify mRNA levels in small numbers of human hepatocytes has been developed for phase I enzymes, phase II enzymes, and transporters. The levels of CYP1A1, CYP2B6, CYP2C8, CYP3A4, CYP3A5, ADH3, and ABCG1 mRNA in human hepatocytes increased after exposure to rifampicin. The levels of CYP1A1, CYP2B6, CYP3A4, CYP3A5, and ABCG1 mRNA recovered after a change to media without rifampicin. The levels of CYP1A1, CYP1A2, CYP1B1, ALDH3, and ALDH6 mRNA increased after exposure to omeprazole, and recovered after a change to media without omeprazole. On the other hand, the levels of ADH3 and ABCB4 mRNA decreased after exposure to omeprazole, and recovered after a change to media without omeprazole. In conclusion, these results demonstrate the applicability of quantitative real-time RT PCR to the evaluation of the gene induction and recovery of drug-metabolizing enzymes and transporters after exposure to drugs in human hepatocytes.

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“…In human mammary gland and uterus, the expression of CYP1B1 has been implicated in 4-hydroxylation of estradiol, a process that may affect estrogen-initiated carcinogenesis by the production of depurinating genotoxic byproducts (27,28). Additionally, for one member of the CYP4 family, CYP4B1, which is mainly expressed extrahepatically in lung and bladder (29), its possible involvement in carcinogenesis by activating 4-ipomeanol (30), 3,3Ј-dichlorobenzidine, and 2-naphthylamine (31) was reported.…”

Section: Introductionmentioning

confidence: 99%

Identification of a Novel Mammary-Restricted Cytochrome P450, CYP4Z1, with Overexpression in Breast Carcinoma

Rieger

Bell²,

Kießling³

et al. 2004

Cancer Research

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By screening a transcriptome database for expressed sequence tags that are specifically expressed in mammary gland and breast carcinoma, we identified a new human cytochrome P450 (CYP), termed CYP4Z1. The cDNA was cloned from the breast carcinoma line SK-BR-3 and codes for a protein of 505 amino acids. Moreover, a transcribed pseudogene CYP4Z2P that codes for a truncated CYP protein (340 amino acids) with 96% identity to CYP4Z1 was found in SK-BR-3. CYP4Z1 and CYP4Z2P genes consisting of 12 exons are localized in head-to-head orientation on chromosome 1p33. Tissue-specific expression was investigated using realtime reverse transcription PCR with normalized cDNA from 18 different human tissues. CYP4Z1 mRNA was preferentially detected in breast carcinoma tissue and mammary gland, whereas only marginal expression was found in all other tested tissues. Investigation of cDNA pairs from tumor/normal tissues obtained from 241 patients, including 50 breast carcinomas, confirmed the breast-restricted expression and showed a clear overexpression in 52% of breast cancer samples. The expression profile of CYP4Z2P was similar to that of CYP4Z1 with preference in breast carcinoma and mammary gland but a lower expression level in general. Immunoblot analyses with a specific antiserum for CYP4Z1 clearly demonstrated protein expression in mammary gland and breast carcinoma tissue specimens as well as in CYP4Z1-transduced cell lines. Confocal laser-scanning microscopy of MCF-7 cells transfected with a fluorescent fusion protein CYP4Z1-enhanced green fluorescent protein and a subcellular fractionation showed localization to the endoplasmic reticulum as an integral membrane protein concordant for microsomal CYP enzymes.

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CYP4B1 Is a Possible Risk Factor for Bladder Cancer in Humans

Cited by 64 publications

References 16 publications

Synergism of aromatic amines and benzo[a]pyrene in induction of Ah receptor-dependent genes

Synergism of aromatic amines and benzo[a]pyrene in induction of Ah receptor-dependent genes

Evaluation of Gene Induction of Drug-Metabolizing Enzymes and Transporters in Primary Culture of Human Hepatocytes Using High-Sensitivity Real-Time Reverse Transcription PCR

Identification of a Novel Mammary-Restricted Cytochrome P450, CYP4Z1, with Overexpression in Breast Carcinoma

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