The P450 Gene Superfamily: Recommended Nomenclature

Nebert, Daniel W.; Adesnik, Milton; Coon, Minor J.; Estabrook, Ronald W.; Gonzalez, Frank J.; Guengerich, F. Peter; Gunsalus, I. C.; Johnson, Eric F.; Kemper, Byron; Levin, Wayne; Phillips, Ian; Sato, Ryo; Waterman, Michael R.

doi:10.1089/dna.1987.6.1

Cited by 744 publications

(255 citation statements)

References 32 publications

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“…The P450 family comprises at least five subfamilies, designated A to E (1). During biotransformation, the coded enzymes mediate phase I reactions in which xenobiotics are activated to reactive intermediate substances.…”

Section: A Leichsenring Et Almentioning

confidence: 99%

CYP1A1 and GSTP1 polymorphisms in an oral cancer case-control study

Leichsenring¹,

Guembarovski²,

Maciel³

et al. 2006

Braz J Med Biol Res

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CYP1A1 and GSTP1 polymorphisms have been associated with a higher risk to develop several cancers, including oral squamous cell carcinoma (OSCC), which is closely related to tobacco and alcohol consumption. Both genes code for enzymes that have an important role in activating or detoxifying carcinogenic elements found in tobacco and other compounds, and polymorphic variants of these genes may result in alterations of the enzymatic activity. The CYP1A1 gene codes for the enzyme aryl hydrocarbon hydroxylase, which is responsible for the metabolism of polycyclic aromatic hydrocarbons. The investigated polymorphism, Ile/Val, seems to increase the activity of the enzyme in homozygous individuals, leading to an accumulation of carcinogens. The Ile/Val polymorphism occurs because of an A→G transition at exon 7, resulting in the CYP1A1*2B allele. The GSTP1*B variant shows an A→G transition at exon 5, changing the amino acid Ile to Val, with a reduced catalytic activity of the enzyme. Due to this reduction, the carriers of mutant alleles lost the capability to metabolize carcinogens, which could be responsible for a higher susceptibility to cancer. We conducted a case-control study in a group of 72 cases with newly diagnosed OSCC and 60 healthy controls matched for age, gender, smoking habits, and ethnicity. We used PCR methods to identify the allelic variants CYP1A1*2B and GSTP1*B. The data obtained showed no statistically significant association of allelic or genotypic variants of CYP1A1*2B (OR = 1.06; 95% CI = 0.49-2.29) and GSTP1*B (OR = 1.40; 95% CI = 0.70-2.79) with OSCC.

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Section: A Leichsenring Et Almentioning

confidence: 99%

CYP1A1 and GSTP1 polymorphisms in an oral cancer case-control study

Leichsenring¹,

Guembarovski²,

Maciel³

et al. 2006

Braz J Med Biol Res

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“…Of these P-450s, P-45Oc (new nomenclature: P-450IA1 [2]) is distributed fairly ubiquitously in various tissues in rats and is induced by the administration of inducers such as 3-methylcholanthrene and 2,3,7,8-tetrachlorodibenzodioxin [3,4]. Severallaboratories have attempted to reveal the molecular mechanisms of the induction phenomena, using the DNA transfection technique [5 -91.…”

mentioning

confidence: 99%

Repression of cytochrome P‐450c gene expression by cotransfection with adenovirus E1a DNA

Sogawa

Handa

Fujisawa‐Sehara

et al. 1989

European Journal of Biochemistry

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Gene expression of rat cytochrome P-45Oc (P-45Oc) depends upon inducible enhancers scattered in the 5'-upstream region of the gene. We show that expression of the P-45Oc gene is repressed by contransfection with adenovirus Ela DNA, regardless of the presence or absence of inducers, in a transient expression system of HeLa cells. Since cotransfection of either 13s or 12s Ela cDNA was effective in the repression, the region necessary for repression could be separated from that of transactivation of other adenovirus early genes. Moreover, we investigated the regions responsible for the inhibitory activity using in-frame deletion mutants lacking internal or external portions of the Ela proteins. The sequence responsible for the repression was located in the aminoterminal half of the Ela proteins. The inducible expression of the chimeric plasmid containing a 24-base-pair enhancer sequence of the P-45Oc gene placed in a heterologous promoter of SV40 was repressed by cotransfection with Ela DNA, suggesting strongly that the inhibitory effect of the Ela proteins upon P-45Oc gene expression was caused by blocking the enhancer activity.Cytochrome P-450 (P-450) constitutes a superfamily and plays an important role in oxidative metabolism of exogenous and endogenous substrates as a terminal oxidase in an NADPH-dependent electron pathway of liver microsomes [l]. Of these P-450s, P-45Oc (new nomenclature: P-450IA1 [2]) is distributed fairly ubiquitously in various tissues in rats and is induced by the administration of inducers such as 3-methylcholanthrene and 2,3,7,8-tetrachlorodibenzodioxin [3,4]. Severallaboratories have attempted to reveal the molecular mechanisms of the induction phenomena, using the DNA transfection technique [5 -91. From these studies, a cis-acting DNA element, responsible for the inducible expression of the gene, was identified within short segments in the upstreamflanking region of the P-45Oc gene and designated XRE (xenobiotic responsive element) [7], although the element is also indispensable for the basal level expression of the P-45Oc gene. Furthermore, this element was found to operate also on a heterologous promoter of SV40 in a manner relatively independent of distance and orientation and is, therefore, classified into the category of inducible enhancers. Several lines of evidence strongly suggest that the inducible expression of the P-45Oc gene after administration of inducers is mediated Correspondence to K. Sogawa, Department of Chemistry, Faculty of Science, Tohoku University, Aobayarna, Sendai-shi Miyagi-ken, Japan 980Abbreviations. P-450c, cytochrome P-45Oc; CAT, chloramphenicol acetyltransferase; XRE, xenobiotic responsive element; Ad, adenovirus.Enzymes. T4 DNA ligase (EC 6.5. [18], were activated by the Ela proteins, while activities of viral enhancers, including SV40 and polyoma virus and cellular enhancer elements such as immunoglobulin-heavychain and insulin genes, were repressed [19-221. We are interested in the mechanism whereby the inducible enhancer of the P-45Oc gene is infl...

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“…Animal studies provided the first unequivocal evidence that cytochrome P450 exists in a number of multiple forms (Lu & West, 1980). One subfamily of the P-450 superfamily is represented by two forms of P-450 which are susceptible to induction by polycyclic aromatic hydrocarbons (the major inductive component of cigarette smoke) and has been named P-450I (Nebert et al, 1987). The two human P-450Is have been isolated and sequenced and shown to be equivalent to animal polycyclic hydrocarboninduced P-450s.…”

Section: Discussionmentioning

confidence: 99%

“…The two human P-450Is have been isolated and sequenced and shown to be equivalent to animal polycyclic hydrocarboninduced P-450s. Anticonvulsant drugs (for which phenobarbitone has been the prototype) are responsible for induction of the distinct subfamily P-4501IB (Nebert et al, 1987). Early studies (Sladek & Mannering, 1969) demonstrated that the effects of the above types of inducers could be additive, at least in animals.…”

Section: Discussionmentioning

confidence: 99%

Theophylline and antipyrine disposition in smoking and non‐smoking epileptic subjects.

Acheson

Uden

Braganza

et al. 1987

Brit J Clinical Pharma

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Theophylline and antipyrine disposition has been compared in smoking epileptic patients, non-smoking epileptic patients and non-smoking healthy volunteers. Although clear differences in drug clearance and half-life were evident as a result of anticonvulsant drug therapy, no effect of smoking was discernible. Thus, additive effects from induction of the hepatic microsomal monooxygenase system in man by anticonvulsant drugs and polycyclic aromatic hydrocarbons (in cigarette smoke) were not evident.

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The P450 Gene Superfamily: Recommended Nomenclature

Cited by 744 publications

References 32 publications

CYP1A1 and GSTP1 polymorphisms in an oral cancer case-control study

CYP1A1 and GSTP1 polymorphisms in an oral cancer case-control study

Repression of cytochrome P‐450c gene expression by cotransfection with adenovirus E1a DNA

Theophylline and antipyrine disposition in smoking and non‐smoking epileptic subjects.

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