Cloning and characterization of cDNAs encoding 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible rabbit mRNAs for cytochrome P-450 isozymes 4 and 6.

Okino, Steve T.; Quattrochi, Linda C.; Barnes, Henry J.; Osanto, S.; Griffin, Keith J.; Johnson, Eric F.; Tukey, Robert H.

doi:10.1073/pnas.82.16.5310

Cited by 48 publications

(23 citation statements)

References 31 publications

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“…However, 78% homology was exhibited toward the predicted amino acid sequence from the rabbit P-450 4 cDNA clone, which encoded 83% of the protein (2). Two base pair changes in our previous sequence of the rabbit P-450 4 cDNA (2) changes leucine-356 to an arginine and isoleucine-461 to a threonine.…”

Section: Resultsmentioning

confidence: 99%

“…It has been proposed that in humans, the gene equivalent to the major CL41Bz2-dioxin-inducible form in rabbit, P-450 4, and its counterparts in mice and rats, P3-450 and P-450d, respectively, does not exist (9). However, our laboratory has shown by DNA sequence analysis of a 600-base-pair (bp) cDNA clone called hpP-450 4, which was identified by hybridization of a rabbit P-450 4 cDNA clone (2) to a human cDNA library, that the human equivalent to rabbit P-450 4 gene is expressed in human liver (11). Southern blot analysis also showed that the P-450 4 and P-450 6 (P1-450) mRNAs were encoded by separate genes.…”

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confidence: 99%

“…(CL4Bz2-dioxin)-inducible P-450 4 and P-450 6 have been shown by DNA sequence analysis to be homologous to rat P-450d and P-450c and mouse P3-450 and P1-450, respectively (2). Rabbit P-450 4 and P-450 6 are differentially regulated during development, with P-450 4 constituting the major adult form in liver while P-450 6 is expressed in other tissues (3,4).…”

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Human cytochrome P-450 4 mRNA and gene: part of a multigene family that contains Alu sequences in its mRNA.

Quattrochi¹,

Pendurthi²,

Okino³

et al. 1986

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

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Several overlapping Xgtll cDNA clones have been sequenced and shown to encode for the full-length human cytochrome P-450 4. The structure and location of the exons and flanking intron regions were also identified from a XEMBL-3 human genomic clone that encodes the full-length human P-450 4 gene. The human P-450 4 mRNA is flanked by 62 base pairs of 5'-and 1508 base pairs of 3'-noncoding sequence, with 1548 bases that encode a protein of 516 amino acids (Mr, 58,376). The predicted amino acid sequence of human P-450 4 is 69% and 70% homologous to its equivalent in mouse and rat, respectively, 75% homologous to rabbit P-450 4, and 68% homologous to human P1-450. The 7.6-kilobase gene encodes 3118 nucleotides of exon sequence that is separated by six introns into seven exons. Exon 7, which is 1802 nucleotides, contains three inverse/complement Alu sequences that are organized in tandem. Comparison of the genomic DNA sequence of the human P-450 4 gene with the human P1-450 and related genes in rat and mouse and the identification of the amino acid residues and triplet codon at each exon-intron junction show that the location of each intron in the human P-450 4 gene is conserved within this gene family. Although the length and homology of the introns within a related gene family may not be conserved, the location of intronic sequences may be an important determinant in the identification of related P-450 genes.The cytochrome P-450 monooxygenases are a group of proteins responsible for the oxidation of drugs, environmental pollutants, and endogenous compounds such as steroids and fatty acids (1). The diversity within this group of enzymes is dictated by structural heterogeneity, tissue specificity, and the differential regulation of the various forms of P-450. One highly conserved subfamily of the P-450 superfamily is represented by two forms of P-450 that are susceptible to induction by polycyclic aromatic hydrocarbons. In rabbits, cDNAs that encode for 2,3,7,8-tetrachlorodibenzo-p-dioxin (CL4Bz2-dioxin)-inducible P-450 4 and P-450 6 have been shown by DNA sequence analysis to be homologous to rat P-450d and P-450c and mouse P3-450 and P1-450, respectively (2). Rabbit P-450 4 and P-450 6 are differentially regulated during development, with P-450 4 constituting the major adult form in liver while P-450 6 is expressed in other tissues (3,4). Similar observations have been made for the homologous forms in the mouse (5). In mice and rats, it has been shown that the induction by C14Bz2-dioxin requires the presence of specific DNA regions on the 5' side of the cap site on the P1-450 and P-450c (6)(7)(8) genes.An important step to understand how this gene family has evolved and what mechanisms control its expression in humans is to characterize the mRNAs and genes that encode this family of P-450s. The cDNA and gene that encode the human equivalent to mouse P1-450 has been fully characterized (9, 10). It has been proposed that in humans, the gene equivalent to the major CL41Bz2-dioxin-inducible form in rabbit, P-450...

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

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Human cytochrome P-450 4 mRNA and gene: part of a multigene family that contains Alu sequences in its mRNA.

Quattrochi¹,

Pendurthi²,

Okino³

et al. 1986

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

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“…Kimura et al, 1984;Okino et al, 1985;Quattrochi et al, 1985). Fish CYP1As share significant sequence similarity with both CYP1A1s and CYP1A2s (Morrison et al, 1995) and display a combination of catalytic functions characteristic of the mammalian isoforms (e.g.…”

Section: Introductionmentioning

confidence: 99%

A Revised Evolutionary History of the CYP1A Subfamily: Gene Duplication, Gene Conversion, and Positive Selection

Goldstone

Stegeman

2006

J Mol Evol

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Running header: Recombination and selection in tetrapod CYP1AsKey words: Cytochrome P450, gene conversion, gene duplication, chicken, mammalian Abbreviations:Page 1 of 32 JME-2005-00134 ABSTRACTMembers of cytochrome P450 subfamily 1A (CYP1As) are involved in detoxification and bioactivation of common environmental pollutants. Understanding the functional evolution of these genes is essential to predicting and interpreting species differences in sensitivity to toxicity by such chemicals. The CYP1A gene subfamily comprises a single ancestral representative in most fish species and two paralogs in higher vertebrates, including birds and mammals.Phylogenetic analysis of complete coding sequences suggests that mammalian and bird paralog pairs (CYP1A1/2 and CYP1A4/5, respectively) are the result of independent gene duplication events. However, comparison of vertebrate genome sequences revealed that CYP1A genes lie within an extended region of conserved fine-scale synteny, suggesting that avian and mammalian CYP1A paralogs share a common genomic history. Algorithms designed to detect recombination between nucleotide sequences indicate that gene conversion has homogenized most of the length of the chicken CYP1A genes, as well as the 5' end of mammalian CYP1As.Together, these data indicate that avian and mammalian CYP1A paralog pairs resulted from a single gene duplication event and that extensive gene conversion is responsible for the exceptionally high degree of sequence similarity between CYP1A4 and CYP1A5. Elevated nonsynonymous/synonymous substitution ratios within a putatively unconverted stretch of ~250 bp suggests that positive selection may have reduced the effective rate of gene conversion in this region, which contains two substrate recognition sites. This work significantly alters our understanding of functional evolution in the CYP1A subfamily, suggesting that gene conversion and positive selection have been the dominant processes of sequence evolution.

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“…In humans, CYP1A1 and 1A2 share 80% amino acid seqence identity and are ~40% identical with CYP1B1 (98)(99)(100)(101). cDNA clones and amino acid sequences of former two enzymes have been characterized in 1985-1986 (98-100), while a human CYP1B1 cDNA clone and amino acid sequence were reported in 1994 (101).…”

Section: T Shimadamentioning

confidence: 99%

Inhibition of Carcinogen-Activating Cytochrome P450 Enzymes by Xenobiotic Chemicals in Relation to Antimutagenicity and Anticarcinogenicity

Shimada

2017

ToxicolRes

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A variety of xenobiotic chemicals, such as polycyclic aromatic hydrocarbons (PAHs), aryl-and heterocyclic amines and tobacco related nitrosamines, are ubiquitous environmental carcinogens and are required to be activated to chemically reactive metabolites by xenobiotic-metabolizing enzymes, including cytochrome P450 (P450 or CYP), in order to initiate cell transformation. Of various human P450 enzymes determined to date, CYP1A1, 1A2, 1B1, 2A13, 2A6, 2E1, and 3A4 are reported to play critical roles in the bioactivation of these carcinogenic chemicals. In vivo studies have shown that disruption of Cyp1b1 and Cyp2a5 genes in mice resulted in suppression of tumor formation caused by 7,12-dimethylbenz[a]anthracene and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, respectively. In addition, specific inhibitors for CYP1 and 2A enzymes are able to suppress tumor formation caused by several carcinogens in experimental animals in vivo, when these inhibitors are applied before or just after the administration of carcinogens. In this review, we describe recent progress, including our own studies done during past decade, on the nature of inhibitors of human CYP1 and CYP2A enzymes that have been shown to activate carcinogenic PAHs and tobacco-related nitrosamines, respectively, in humans. The inhibitors considered here include a variety of carcinogenic and/or non-carcinogenic PAHs and acethylenic PAHs, many flavonoid derivatives, derivatives of naphthalene, phenanthrene, biphenyl, and pyrene and chemopreventive organoselenium compounds, such as benzyl selenocyanate and benzyl selenocyanate; o-XSC, 1,2-, 1,3-, and 1,4-phenylenebis(methylene)selenocyanate.

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Cloning and characterization of cDNAs encoding 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible rabbit mRNAs for cytochrome P-450 isozymes 4 and 6.

Cited by 48 publications

References 31 publications

Human cytochrome P-450 4 mRNA and gene: part of a multigene family that contains Alu sequences in its mRNA.

Human cytochrome P-450 4 mRNA and gene: part of a multigene family that contains Alu sequences in its mRNA.

A Revised Evolutionary History of the CYP1A Subfamily: Gene Duplication, Gene Conversion, and Positive Selection

Inhibition of Carcinogen-Activating Cytochrome P450 Enzymes by Xenobiotic Chemicals in Relation to Antimutagenicity and Anticarcinogenicity

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