More than one neoplastic founder clone can exist in benign epithelial tumours. Although theories of clonal selection make pluriclonality appear unlikely in carcinomas, published data do not exclude this possibility. This study looked for evidence of multiclonal X inactivation in ovarian carcinoma using AR methylation as a marker. Fifteen unifocal ovarian carcinomas and 14 multifocal carcinomas all in Scottish patients were studied. One representative formalin-fixed paraffin-embedded tumour block was chosen for each of the former and two for the latter. From each of these 43 tumour blocks three samples each of approximately 10(4) carcinoma cells were obtained by microdissection (129 in all). DNA released by proteinase K digestion was subjected to PCR amplification of the androgen receptor gene AR exon I CAG repeat polymorphism with and without prior digestion with methylation-sensitive restriction enzymes HpaII and HhaI. Complex amplification patterns were consistent with mosaic X inactivation in some ovarian carcinomas but acquired anomalies of AR methylation cannot be excluded. Parallel analysis of other X-linked polymorphic loci would strengthen the inference of clonality status from DNA methylation data in tumour X studies. Strikingly, the number of CAG repeats in the 29 ovarian tumour patients (median 16, range 11 - 20) was substantially fewer than in 34 previously studied breast cancer patients from the same scottish population (median 21, range 14 - 26; P < 0.0001), and women homozygous for the AR CAG repeat were over-represented in the ovarian cancer patients but not in the breast cancer series. These findings reinforce recent suggestions that AR may have a role in ovarian carcinogenesis.

The human tumour suppressor gene PTEN located at 10q23 is mutated in a variety of tumour types particularly metastatic cases and in the germline of some individuals with Cowdens cancer predisposition syndrome. We have assessed the status of PTEN and associated pathways in cell lines derived from 19 squamous cell carcinomas of the head and neck. Loss of heterozygosity is evident at, or close to the PTEN gene in 5 cases, however there were no mutations in the remaining alleles. Furthermore by Western analysis PTEN protein levels are normal in all of these SCC-HN tumours and cell lines. To assess the possibility that PTEN may be inactivated by another mechanism, we characterized lipid phosphatase levels and from a specific PIP3 biochemical assay it is clear that PTEN is functionally active in all 19 human SCCs. Our data strongly suggest the possibility that a tumour suppressor gene associated with development of SCC-HN, other than PTEN, is located in this chromosomal region. This gene does not appear to be MXI-1, which has been implicated in some other human tumour types. PTEN is an important negative regulator of PI3Kinase, of which subunit alpha is frequently amplified in SCC-HN. To examine the possibility that PI3K is upregulated by amplification in this tumour set we assessed the phosphorylation status of Akt, a downstream target of PI3K. In all cases there is no detectable increase in Akt phosphorylation. Therefore there is no detectable defect in the PI3K pathway in SCC-HN suggesting that the reason for 3q26.3 over-representation may be due to genes other than PI3K110α. © 2001 Cancer Research Campaign http://www.bjcancer.com

Tumours are usually considered as the clonal progeny of single transformed cells. An X‐chromosome inactivation assay has been applied to exploring clonal relationships in human breast cancer. Analysis of X‐inactivation in DNA extracted from microdissected in situ and invasive breast carcinoma by Hpa II restriction and polymerase chain reaction (PCR) of the androgen receptor exon I CAG polymorphism confirmed monoclonality in 105/133 samples of carcinoma cells from 31/32 informative breast cancers. Clonality was identical in seven cases between in situ and invasive carcinoma. Unexpectedly, 4 of 12 cancers (33%) with two or more monoclonal samples available were mosaic (polyclonal) in respect of X‐chromosome inactivation between separate morphologically homogeneous tumour cell samples. Concordant clonality supports a common clonal origin of in situ and invasive breast cancers, but frequent apparently mosaic X‐inactivation in breast cancer cannot be explained by non‐tumour cell contamination. It is concluded that these carcinomas may be genuinely multiclonal. Possible mechanisms of multiclonality include simultaneous transformation of cell groups straddling X‐chromosome inactivation patch boundaries, tumour‐initiating mutations prior to X‐inactivation, or recruitment of bystander stem cells by DNA transfer from necrotic or apoptotic tumour cells. Collision of independent cancers appears implausible at this frequency. Further studies using independent analytical techniques are required to test the important possibility that a significant proportion of mammary carcinomas are not monoclonal. Copyright © 2001 John Wiley & Sons, Ltd.

The cytochrome P450 isoforms responsible for the regio-selective metabolism of benz[a]anthracene (BA) are poorly defined but as with other polycyclic aromatic hydrocarbons (PAHs) may include members of the CYP2C sub-family. Since the expression of some of these is regulated in a gender-specific manner and may be altered by age, rat strain or by phenobarbital treatment, the effects of these variables on metabolism of BA to diols was investigated. These studies used hepatic, microsomal membranes from immature and adult Long-Evans rats and adult Hooded Lister rats. BA-diols were resolved by normal phase HPLC into three discrete peaks identified as benz[a]anthracene-5,6-diol (BA-5,6-diol), benz[a]anthracene-10, 11-diol (BA-10,11-diol) and a mixture of benz[a]anthracene-3,4- and -8,9-diols (BA-3,4-diol and BA-8,9-diol and termed Peak(3/8)). Significant gender-related differences were found in the rates of diol formation in adults of both the Long-Evans and Hooded Lister rat strains. Formation of BA-10,11-diol and to a lesser extent the components of Peak(3/8) were greater in the male compared to female animals by factors of at least 14 and two, respectively. An age-dependent effect is also observed in the Long-Evans rat since these differences are still apparent in prepubertal animals but to a lesser extent (gender ratio male:female BA-10,11-diol 9X; Peak(3/8) 1.4X). In contrast BA-5,6-diol was formed at similar rates by membranes from female and male rats whether mature (Long-Evans and Hooded Lister) or immature (Long-Evans). Phenobarbital treatment of the adult Long-Evans rats resulted in a moderate increase in the formation of each diol other than at the 10,11-position and the induction was not gender specific. The rate of formation of BA-10, 11-diol was decreased in phenobarbital-treated male rats suggesting modulation of a male specific isoform. Measurement of microsomal epoxide hydrolase revealed no gender or age differences and suggests that this enzyme is not rate limiting in BA-diol formation and thus is not responsible for the differences in BA-diol formation observed. The results suggest that CYP2C11 along with a male-specific isoenzyme not regulated by age are important in the formation of BA-10,11-diol and a component(s) of Peak(3/8) in males. CYPs 2B2 and/or 2C6 appear to be involved in formation of BA-5,6-diol in male and female. Identification of the CYPs involved in the regio-selective metabolism of BA may lead to an explanation of the lower carcinogenic potency of this PAH compared to dimethylbenz[a]anthracene and this study provides novel clues concerning the identities of the CYPs, which are important.

The effects of age, gender, strain, phenobarbital (PB) treatment and pituitary influence on the regioselective metabolism of 7, 12-dimethylbenz[a]anthracene to hydroxmethyl metabolites were investigated. Studies used hepatic microsomal membranes from immature and mature Long Evans (LE) rats and adult Hooded Lister (HL) animals. Hydroxymethyl metabolites were resolved by both normal and reverse phase HPLC with on-line diode array detection. The CYP isoform(s) responsible for oxidation at the 12 methyl position exhibited no gender or developmental regulation and the rate of formation was not altered following hypophysectomy. PB-treatment of adult rats caused a significant increase in the rate of formation of both male and female animals (29 and 41-fold, respectively) suggesting a major contribution from a PB-inducible isoform, such as CYP2B. The rate of formation of 7OHMe12MBA exhibited no gender dependency in immature animals but was 2-fold greater than that observed for 12OHMe7MBA suggesting that steric hindrance resulting from the adjacent 1,2 benzyl ring favours substrate oxidation at the 7-methyl position. Male predominant formation of 7OHMe12MBA was apparent following sexual maturation of the LE rats and was significantly reduced upon hypophysectomy suggesting the involvement of a male-specific GH dependent isoform e.g. CYP2C11.

The metabolism of polycyclic aromatic hydrocarbons by bone marrow, mononuclear cells from normal donors and leukaemia patients in remission has been investigated. When benz[alpha]anthracene (BA) was included with marrow under cell culture conditions, it was converted to materials which were resolved into three peaks by normal phase HPLC, and which had the chromatographic characteristics of BA-dihydrodiols. Formation of hydroxymethyl-or dihydrodiol-derivatives of 7, 12-dimethylbenz[alpha]anthracene were not detected under the same conditions. The BA-metabolites were identified as BA-5,6-dihydrodiol, BA-10,11-dihydrodiol and BA-8,9-dihydrodiol. The identification was based upon chromatographic properties of the metabolites during normal and reverse phase chromatography and on UV spectral and fluorometric characterization. It was not possible to detect the formation of BA-3,4-dihydrodiol since this dihydrodiol co-elutes with BA-8,9-dihydrodiol and BA-10,11-dihydrodiol during normal phase and reverse phase chromatography, respectively. the UV spectra of BA-3,4-dihydrodiol does not have features which enable it to be readily identified in the presence of these other compounds. Formation of the dihydrodiol-metabolites was dependent on cell number and temperature. Two general cytochrome P450 inhibitors, carbon monoxide and piperonyl butoxide, blocked the formation of metabolites but the cyclooxygenase inhibitor, indomethacin had no effect. Large variations were observed in the capacity of marrow from different individuals to form benz[alpha]anthracene-dihydrodiols but, in each sample where dihydrodiols were formed, the relative amount of each metabolite was BA-8,9-dihydrodiol >> BA-5,6-dihydrodiol > BA-10,11-dihydrodiol. Factors which may contribute to this variation, including disease status, genetic and environmental agents, are considered.

Previous work has shown that member(s) of the cytochrome P450IIC sub-family play significant roles in the formation of diols of 7,12-dimethylbenz[a]anthracene (DMBA) and are particularly important in formation of the proximate carcinogen (DMBA-3,4-diol). To further characterize the role of members of this subfamily in DMBA-diol formation and to assess the part played by other P450s, DMBA metabolism has been investigated in microsomes prepared from animals pre-treated with isoenzyme selective inducers. The rates of formation of DMBA-diols in membranes from phenobarbital-treated rats were very low when NADH was used as reductant and rates were not altered when NADPH and NADH were used in combination rather than using NADPH alone. This suggests that cytochrome b5 is not involved in DMBA-diol formation in these membranes. Treatment of animals with clofibrate, pyrazole and dexamethasone produced regio-selective alterations in the rates of formation of DMBA-diols at the -3,4-, -5,6- and -8,9- positions. However, none of the inducers caused increases in the rates of DMBA-diol formation of any great magnitude suggesting that the isoforms which are the major induced proteins (P450IVA1, P450IIE1 and P450IIIA1) do not play a significant role in diol formation. The content of other P450s in these membrane are also altered and these were investigated by Western blot using antibodies to P450IIC6, P450IIB1 and P450IIIA1. The results of the Western blots show that the effects of the inducing agents on DMBA-diol formation can be explained by alterations of members of the P450IIC and P450IIB subfamilies.

The role of specific cytochrome P450 (P450) isoforms in the formation of adducts of 7,12-dimethylbenz(a)anthracene metabolites and membrane proteins has been investigated in vitro with microsomal fractions prepared from rats pretreated with various isoenzyme selective inducers. The effects of isoenzyme selective inhibitors were also evaluated. Adduct formation was shown to be mediated by P450 catalysed reactions but was unaltered, relative to untreated animals, in membranes from pyrazole- and clofibrate-treated animals suggesting that CYP2E1 and CYP4A1 are not involved in this process. However, adduct formation was significantly increased in microsomes from Sudan III-, phenobarbital- and dexamethasone-treated rats, suggesting the involvement of the CYP1A, CYP2B and CYP3A subfamilies, respectively. These conclusions were further supported by the finding that adduct formation in these microsomes could be inhibited by the isoenzyme-selective inhibitors alpha-naphthoflavone, metyrapone and troleandomycin, respectively.

The role of specific cytochrome P-450 isoenzymes in the regio-selective metabolism of 7,12-dimethylbenz[a]anthracene (DMBA) has been studied in microsomal membranes from rat and human liver. An antibody inhibition study using membranes from phenobarbital-treated rats demonstrates that a member(s) of the CYP2C family accounts for up to 90% of the formation of the proximate carcinogen, DMBA-3,4-diol, and makes significant contributions to the formation of DMBA-5,6-diol and DMBA-8,9-diol. In these membranes the formation of DMBA-5,6-diol can be entirely accounted by the combined activity of members of the CYP2C and CYP2B families. The metabolism of DMBA has been investigated in human using microsomes from 10 individuals and the metabolites formed by these membranes were found to be mainly hydroxymethyl- and -diol products. The rates of formation of each metabolite show considerable interindividual variation and there was no correlation between these rates for any pairing of metabolites. The CYP content in these membranes of specific members of families 1, 2, 3 and 4 did correlate with the rates of formation of individual metabolites. Surprisingly there was no correlation between the content of CYP2C and formation of DMBA-3,4-diol but an antibody to rat CYP2C6 partially inhibited the formation of this metabolite. The results indicate that in human both inducible sub-families of CYPs, particularly of the PB-type, and constitutively expressed CYPs may be important in DMBA metabolism and that each metabolite may be produced by the combined activity of several CYP isoforms.

Infection of mice with Leishmania donovani resulted in decreased activities of several liver enzymes involved in the metabolism of xenobiotics. Microsomal membranes from infected livers contained reduced amounts of cytochromes P450 and b5 and NADPH-cytochrome P450 reductase. Several cytochrome P450 isoenzymes (P450-PB1, P450-PB3, P450-PCN and P450-UT1) and P450-mediated reactions (aminopyrine demethylase, aniline hydroxylase, benzphentamine demethylase and ethoxycoumarin deethylase) were affected similarly. The metabolism of two carcinogens (nitrosodimethylamine and 7,12-dimethylbenz[a]anthracene) by liver microsomal membrane preparations was also reduced. Leishmania infection caused an increase of cytosolic epoxide hydrolase and microsomal epoxide hydrolase and NADH-cytochrome b5 reductase were unaffected. The results suggest that Leishmania-infected animals are likely to have altered responses to exogenous toxins compared to uninfected animals.

Conference Article| December 01 1989 Metabolic activation of 7,12-dimethylbenz(a)anthracene: role of cytochrome P-450 isoenzymes in the formation of DNA and protein adducts in vitro M. CUSACK; M. CUSACK *Department of Biological Sciences, Glasgow College, Glasgow G4 0BA, U.K. Search for other works by this author on: This Site PubMed Google Scholar A. K. BURNETT; A. K. BURNETT †Leukaemia Research Fund Laboratories, Glasgow Royal Infirmary, Glasgow G4 0SF, U.K. Search for other works by this author on: This Site PubMed Google Scholar V. M. MORRISON; V. M. MORRISON *Department of Biological Sciences, Glasgow College, Glasgow G4 0BA, U.K. Search for other works by this author on: This Site PubMed Google Scholar J. A. CRAFT J. A. CRAFT *Department of Biological Sciences, Glasgow College, Glasgow G4 0BA, U.K. Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1989) 17 (6): 1014–1015. https://doi.org/10.1042/bst0171014 Article history Received: June 19 1989 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation M. CUSACK, A. K. BURNETT, V. M. MORRISON, J. A. CRAFT; Metabolic activation of 7,12-dimethylbenz(a)anthracene: role of cytochrome P-450 isoenzymes in the formation of DNA and protein adducts in vitro. Biochem Soc Trans 1 December 1989; 17 (6): 1014–1015. doi: https://doi.org/10.1042/bst0171014 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search Keywords: P-450, cytochrome P-450, DMBA, 7,12-dimethylbenz[a]anthracene, DO, 3,4-diol-1,2-oxide This content is only available as a PDF. © 1989 Biochemical Society1989 Article PDF first page preview Close Modal You do not currently have access to this content.

Nitrosomethylethylamine and nitrosomethylpropylamine were found to be more potent inducers of rat liver microsomal epoxide hydrolase (styrene oxide hydrolase) than nitrosodiethylamine or nitrosodimethylamine. The time course of induction following a single administration of nitrosodimethylethylamine, nitrosomethylpropylamine or nitrosodiethylamine each showed a delay of 24 hr during which enzyme activity was unaltered. After that time activity increased and reached a maximum at between 72 and 120 hr. Increased enzyme activity following NDEA was paralleled by changes in the content of epoxide hydrolase in microsomes as measured by Western blots. Nitrosamines caused an increase of mRNA for epoxide hydrolase which was detected by probing Northern blots with a [32]-P labelled epoxide hydrolase cDNA and by in vitro translation of polyadenylated mRNA. Both methods showed a maximal increase at 72 hr after nitrosodiethylamine treatment but a significant increase was also observed at 24 hr although at this time no increase in enzyme activity was apparent.

The rates of formation of diols of dimethylbenz[a]anthracene (DMBA-3,4-diol, DMBA-5,6-diol and DMBA-8,9-diol) have been determined in hepatic microsomes prepared from untreated rats or from animals treated with phenobarbital (PB) or Sudan III. PB treatment enhanced the formation of the proximate carcinogen, DMBA-3,4-diol, and of the 5,6-diol while treatment with Sudan III suppressed the formation of DMBA-3,4-diol but greatly increased the rates of formation of the other two diols. Metyrapone, a reagent which is specific for members of the major PB-induced cytochrome P-450 subfamily (P-450-PB3), did not alter the rate of formation of the diols other than in microsomes prepared from PB-treated animals in which formation of the 5,6-diol was inhibited. Incubation of DMBA with microsomes resulted in the formation of covalent, DMBA-microsome adducts. Treatment of the animals with PB and Sudan III increased the rate of formation of DMBA-microsome adducts to a similar extent (approximately 5-fold). The formation of adducts could be inhibited by metyrapone in microsomes from untreated and PB-treated animals but the reagent had no effect on adduct formation in microsomes from Sudan III-treated animals. These observations may indicate that adduct formation in microsomes from Sudan-treated animals involves primary epoxide metabolites while in microsomes from PB-treated animals secondary metabolites are involved and these may be formed by a P-450-PB3 isoenzyme. Specific P-450 isoenzymes involved in the regioselective formation of DMBA-diols have been identified by the use of antibodies directed against specific isoenzymes. An antibody to P-450-MC1b inhibited the formation of DMBA-5,6-diol and 8,9-diol in microsomes from Sudan III-treated animals. Western blot analysis demonstrated that P-450-MC1b was induced in microsomes of animals treated with Sudan III but was not present in the other two microsomal preparations. In accord with the observations with metyrapone, anti-P-450-PB3 inhibited formation of DMBA-5,6-diol in microsomes from PB-treated animals but was without effect on the formation of other diols. Anti-P450-PB1 inhibited the formation of DMBA-3,4-diol in microsomes from PB-treated animals. Western blot analysis of microsomes from animals treated with several xenobiotics indicated a qualitative correlation between the content of P-450-PB1 and the rate at which DMBA-3,4-diol was formed.

Conference Article| August 01 1987 Partial nucleotide sequence of a cloned cDNA for human liver microsomal epoxide hydrolase JOHN A. CRAFT; JOHN A. CRAFT *Department of Biological Sciences, Glasgow College of Technology, Glasgow G4 OBA, U.K. Search for other works by this author on: This Site PubMed Google Scholar MICHAEL R. JACKSON; MICHAEL R. JACKSON †Department of Biochemistry, The University, Dundee DD1 4HN, Scotland, U.K. Search for other works by this author on: This Site PubMed Google Scholar BRIAN BURCHELL BRIAN BURCHELL *Department of Biological Sciences, Glasgow College of Technology, Glasgow G4 OBA, U.K. Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1987) 15 (4): 708–709. https://doi.org/10.1042/bst0150708a Article history Received: December 01 1986 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Cite Icon Cite Get Permissions Citation JOHN A. CRAFT, MICHAEL R. JACKSON, BRIAN BURCHELL; Partial nucleotide sequence of a cloned cDNA for human liver microsomal epoxide hydrolase. Biochem Soc Trans 1 August 1987; 15 (4): 708–709. doi: https://doi.org/10.1042/bst0150708a Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search Keywords: mEH, microsomal epoxide hydroxylase, PAH, polycyclic aromatic hydrocarbons, RmEH, rat mEH, HmEH, human mEH This content is only available as a PDF. © 1987 Biochemical Society1987 Article PDF first page preview Close Modal You do not currently have access to this content.

Microsomal epoxide hydrolase was purified from rat liver, and different fractions of the purified enzyme, which varied in their contents of phospholipid, were obtained by ion-exchange chromatography. One fraction (A), which did not bind to CM-cellulose, had a high phospholipid content, and a second fraction (B), which was eluted from CM-cellulose at high ionic strength, had a low phospholipid content. Removal of most of the phospholipid from fraction A altered its chromatographic behaviour. When the delipidated material was re-applied to CM-cellulose, most of the enzyme bound to the cation-exchanger. The specific activities of all the fractions described (with styrene epoxide [(1,2-epoxyethyl)benzene] as substrate) were altered by adding the non-ionic detergent Lubrol PX or phospholipid. Lubrol PX inhibited enzyme activity, and phospholipid reversed this inhibition. The various enzyme fractions isolated appeared to be different forms of the same protein, as judged by their minimum Mr values and immunochemical properties. These results indicate that different fractions of epoxide hydrolase isolated by ion-exchange chromatography probably are not different isoenzyme forms.

Conference Article| October 01 1986 Nitrosodiethylamine increases mRNA encoding rat hepatic microsomal epoxide hydrolase N. J. BULLEID; N. J. BULLEID 1Department of Biological Sciences, Glasgow College of Technology, Glasgow G4 0BA, U.K. Search for other works by this author on: This Site PubMed Google Scholar J. A. CRAFT J. A. CRAFT 1Department of Biological Sciences, Glasgow College of Technology, Glasgow G4 0BA, U.K. Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1986) 14 (5): 881–882. https://doi.org/10.1042/bst0140881 Article history Received: March 21 1986 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation N. J. BULLEID, J. A. CRAFT; Nitrosodiethylamine increases mRNA encoding rat hepatic microsomal epoxide hydrolase. Biochem Soc Trans 1 October 1986; 14 (5): 881–882. doi: https://doi.org/10.1042/bst0140881 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search This content is only available as a PDF. © 1986 Biochemical Society1986 Article PDF first page preview Close Modal You do not currently have access to this content.

Conference Article| April 01 1985 Effects of metyrapone and norharmane on microsomal mono-oxygenase and epoxide hydrolase activities NEIL J. BULEID; NEIL J. BULEID 1Department of Biological Sciences, Glasgow College of Technology, Cowcaddens Road, Glasgow G4 0BA, U.K. Search for other works by this author on: This Site PubMed Google Scholar JOHN A. CRAFT JOHN A. CRAFT 2Department of Biological Sciences, Glasgow College of Technology, Cowcaddens Road, Glasgow G4 0BA, U.K. Search for other works by this author on: This Site PubMed Google Scholar Author and article information Publisher: Portland Press Ltd Online ISSN: 1470-8752 Print ISSN: 0300-5127 © 1985 Biochemical Society1985 Biochem Soc Trans (1985) 13 (2): 356. https://doi.org/10.1042/bst0130356 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Citation NEIL J. BULEID, JOHN A. CRAFT; Effects of metyrapone and norharmane on microsomal mono-oxygenase and epoxide hydrolase activities. Biochem Soc Trans 1 April 1985; 13 (2): 356. doi: https://doi.org/10.1042/bst0130356 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search This content is only available as a PDF. © 1985 Biochemical Society1985 Article PDF first page preview Close Modal You do not currently have access to this content.