Kinds and spectrum of mutations induced by 1-nitrosopyrene adducts during plasmid replication in human cells.

Abstract:

:1-Nitropyrene has been shown in bacterial assays to be the principal mutagenic agent in diesel emission particulates. It has also been shown to be mutagenic in human fibroblasts and carcinogenic in animals. To investigate the kinds of mutations induced by this carcinogen and compare them with those induced by a structurally related carcinogen, (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetra-hydrobenzo [a]pyrene (BPDE) (J.-L. Yang, V. M. Maher, and J. J. McCormick, Proc. Natl. Acad. Sci. USA 84:3787-3791, 1987), we treated a shuttle vector with tritiated 1-nitrosopyrene (1-NOP), a carcinogenic mutagenic intermediate metabolite of 1-nitropyrene which forms the same DNA adduct as the parent compound, and introduced the plasmids into a human embryonic kidney cell line, 293, for DNA replication to take place. The treated plasmid, pZ189, carrying a bacterial suppressor tRNA target gene, supF, was allowed 48 h to replicate in the human cells. Progeny plasmids were then rescued, purified, and introduced into bacteria carrying an amber mutation in the beta-galactosidase gene in order to detect those carrying mutations in the supF gene. The frequency of mutants increased in direct proportion to the number of DNA-1-NOP adducts formed per plasmid. At the highest level of adduct formation tested, the frequency of supF mutants was 26 times higher than the background frequency of 1.4 X 10(-4). DNA sequencing of 60 unequivocally independent mutant derived from 1-NOP-treated plasmids indicated that 80% contained a single base substitution, 5% had two base substitutions, 4% had small insertions or deletions (1 or 2 base pairs), and 11% showed a deletion or insertion of 4 or more base pairs. Sequence data from 25 supF mutants derived from untreated plasmids showed that 64% contained deletions of 4 or more base pairs. The majority (83%) of the base substitution in mutants from 1-NOP-treated plasmids were transversions, with 73% of these being G . C --> T . A. This is very similar to what we found previously in this system, using BPDE, but each carcinogen produced its own spectrum of mutations. Of the five hot spots for base substitution mutations produced in the supF gene with 1-NOP, two were the same as seen with BPDE-treated plasmids. However, the three other hot spots were cold spots for BPDE-treated plasmids. Conversely, four of the other five hot spots seen with BPDE-treated plasmids were cold spots for 1-NOP-treated plasmids. Comparison of the two carcinogens for the frequency of supF mutants induced per DNA adduct showed that 1-NOP-induced adducts were 3.8 times less than BPDE adducts. However, the 293 cell excised 1-NOP-induced adducts faster than BPDE adducts.

journal_name

Mol Cell Biol

authors

Yang JL,Maher VM,McCormick JJ

doi

10.1128/mcb.8.8.3364

subject

Has Abstract

pub_date

1988-08-01 00:00:00

pages

3364-72

issue

8

eissn

0270-7306

issn

1098-5549

journal_volume

8

pub_type

杂志文章
  • Kinds of mutations formed when a shuttle vector containing adducts of benzo[a]pyrene-7,8-diol-9,10-epoxide replicates in COS7 cells.

    abstract::We have investigated the kinds of mutations induced when a shuttle vector containing covalently bound residues of the (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) replicates in the monkey kidney cell line COS7. The target for detecting mutations was the 200-base pair g...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.7.3.1267

    authors: Yang JL,Maher VM,McCormick JJ

    更新日期:1987-03-01 00:00:00

  • Elements involved in S-adenosylmethionine-mediated regulation of the Saccharomyces cerevisiae MET25 gene.

    abstract::In Saccharomyces cerevisiae, the MET25 gene encodes O-acetylhomoserine sulfhydrylase. Synthesis of this enzyme is repressed by the presence of S-adenosylmethionine (AdoMet) in the growth medium. We identified cis elements required for MET25 expression by analyzing small deletions in the MET25 promoter region. The resu...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.9.8.3292

    authors: Thomas D,Cherest H,Surdin-Kerjan Y

    更新日期:1989-08-01 00:00:00

  • Impaired adipogenesis caused by a mutated thyroid hormone alpha1 receptor.

    abstract::Thyroid hormone (T3) is critical for growth, differentiation, and maintenance of metabolic homeostasis. Mice with a knock-in mutation in the thyroid hormone receptor alpha gene (TRalpha1PV) were created previously to explore the roles of mutated TRalpha1 in vivo. TRalpha1PV is a dominant negative mutant with a framesh...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.02189-06

    authors: Ying H,Araki O,Furuya F,Kato Y,Cheng SY

    更新日期:2007-03-01 00:00:00

  • Nuclear alpha NAC influences bone matrix mineralization and osteoblast maturation in vivo.

    abstract::Nascent-polypeptide-associated complex and coactivator alpha (alpha NAC) is a protein shuttling between the nucleus and the cytoplasm. Upon phosphorylation at residue serine 43 by integrin-linked kinase, alpha NAC is translocated to the nuclei of osteoblasts, where it acts as an AP-1 coactivator to increase osteocalci...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00378-09

    authors: Meury T,Akhouayri O,Jafarov T,Mandic V,St-Arnaud R

    更新日期:2010-01-01 00:00:00

  • Translation and membrane insertion of the hemagglutinin-neuraminidase glycoprotein of Newcastle disease virus.

    abstract::The hemagglutinin-neuraminidase (HN) protein of paramyxoviruses is likely in the unusual class of glycoproteins with the amino terminus cytoplasmic and the carboxy terminus lumenal or external to the cell. The properties of the membrane insertion of the HN protein of Newcastle disease virus, a prototype paramyxovirus,...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.7.4.1386

    authors: Wilson C,Gilmore R,Morrison T

    更新日期:1987-04-01 00:00:00

  • Selective translational regulation of ribosomal protein gene expression during early development of Drosophila melanogaster.

    abstract::We have previously characterized a cloned cDNA coding for a developmentally regulated mRNA in Drosophila melanogaster whose expression is selectively regulated at the translational level during oogenesis and embryogenesis. In this report we show that this translationally regulated mRNA (rpA1) codes for an acidic ribos...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.5.12.3583

    authors: Kay MA,Jacobs-Lorena M

    更新日期:1985-12-01 00:00:00

  • Kinetics and regulation of the tyrosine phosphorylation of epidermal growth factor receptor in intact A431 cells.

    abstract::We have previously reported that antibodies to phosphotyrosine recognize the phosphorylated forms of platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) receptors (Zippel et al., Biochim. Biophys. Acta 881:54-61, 1986, and Sturani et al., Biochem. Biophys. Res. Commun. 137:343-350, 1986). In this r...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.3.1345

    authors: Sturani E,Zippel R,Toschi L,Morello L,Comoglio PM,Alberghina L

    更新日期:1988-03-01 00:00:00

  • A carboxy-terminal basic region controls RNA polymerase III transcription factor activity of human La protein.

    abstract::Human La protein has been shown to serve as a transcription factor for RNA polymerase III (pol III) by facilitating transcription termination and recycling of transcription complexes. In addition, La binds to the 3' oligo(U) ends common to all nascent pol III transcripts, and in the case of B1-Alu RNA, protects it fro...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.10.5823

    authors: Goodier JL,Fan H,Maraia RJ

    更新日期:1997-10-01 00:00:00

  • Functional analysis of the Mad1-mSin3A repressor-corepressor interaction reveals determinants of specificity, affinity, and transcriptional response.

    abstract::The recruitment of corepressors by DNA-bound repressors is likely to be a critical rate-limiting step in the transcriptional regulation of many genes. An excellent paradigm for such an interaction is the association of the basic helix-loop-helix zipper protein Mad1 with the corepressor mSin3A. When bound together, the...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.24.7.2698-2709.2004

    authors: Cowley SM,Kang RS,Frangioni JV,Yada JJ,DeGrand AM,Radhakrishnan I,Eisenman RN

    更新日期:2004-04-01 00:00:00

  • p53-mediated DNA repair responses to UV radiation: studies of mouse cells lacking p53, p21, and/or gadd45 genes.

    abstract::Human cells lacking functional p53 exhibit a partial deficiency in nucleotide excision repair (NER), the pathway for repair of UV-induced DNA damage. The global genomic repair (GGR) subpathway of NER, but not transcription-coupled repair (TCR), is mainly affected by p53 loss or inactivation. We have utilized mouse emb...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.10.3705-3714.2000

    authors: Smith ML,Ford JM,Hollander MC,Bortnick RA,Amundson SA,Seo YR,Deng CX,Hanawalt PC,Fornace AJ Jr

    更新日期:2000-05-01 00:00:00

  • Promoter and enhancer elements from the rat elastase I gene function independently of each other and of heterologous enhancers.

    abstract::An elastase-human growth hormone (hGH) fusion gene containing 205 base pairs of elastase 5' flanking region is expressed exclusively in pancreatic acinar cells of transgenic mice. This paper shows that the promoter region (-72 to +8) and the enhancer (-205 to -73) function independently of each other. The elastase enh...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.7.10.3466

    authors: Ornitz DM,Hammer RE,Davison BL,Brinster RL,Palmiter RD

    更新日期:1987-10-01 00:00:00

  • ZNF536, a novel zinc finger protein specifically expressed in the brain, negatively regulates neuron differentiation by repressing retinoic acid-induced gene transcription.

    abstract::Neuronal differentiation is tightly regulated by a variety of factors. In a search for neuron-specific genes, we identified a highly conserved novel zinc finger protein, ZNF536. We observed that ZNF536 is most abundant in the brain and, in particular, is expressed in the developing central nervous system and dorsal ro...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00362-09

    authors: Qin Z,Ren F,Xu X,Ren Y,Li H,Wang Y,Zhai Y,Chang Z

    更新日期:2009-07-01 00:00:00

  • Analysis of primary structural determinants that distinguish the centromere-specific function of histone variant Cse4p from histone H3.

    abstract::Cse4p is a variant of histone H3 that has an essential role in chromosome segregation and centromere chromatin structure in budding yeast. Cse4p has a unique 135-amino-acid N terminus and a C-terminal histone-fold domain that is more than 60% identical to histone H3 and the mammalian centromere protein CENP-A. Cse4p a...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.19.9.6130

    authors: Keith KC,Baker RE,Chen Y,Harris K,Stoler S,Fitzgerald-Hayes M

    更新日期:1999-09-01 00:00:00

  • Immunologically distinct p53 molecules generated by alternative splicing.

    abstract::Transfection of a functional cloned p53 gene into an L12 p53 nonproducer cell line efficiently reconstituted p53 expression. The p53 protein synthesized in these clones was indistinguishable from that occurring naturally in tumor cells. When a p53 cDNA clone was used instead, we observed that the L12-derived clones ex...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.6.9.3232

    authors: Arai N,Nomura D,Yokota K,Wolf D,Brill E,Shohat O,Rotter V

    更新日期:1986-09-01 00:00:00

  • Erk5 participates in neuregulin signal transduction and is constitutively active in breast cancer cells overexpressing ErbB2.

    abstract::The four receptor tyrosine kinases of the ErbB family play essential roles in several physiological processes and have also been implicated in tumor generation and/or progression. Activation of ErbB1/EGFR is mainly triggered by epidermal growth factor (EGF) and other related ligands, while activation of ErbB2, ErbB3, ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.22.1.270-285.2002

    authors: Esparís-Ogando A,Díaz-Rodríguez E,Montero JC,Yuste L,Crespo P,Pandiella A

    更新日期:2002-01-01 00:00:00

  • A conserved docking motif for CK1 binding controls the nuclear localization of NFAT1.

    abstract::In resting cells, the NFAT1 transcription factor is kept inactive in the cytoplasm by phosphorylation on multiple serine residues. These phosphorylated residues are primarily contained within two types of serine-rich motifs, the SRR-1 and SP motifs, which are conserved within the NFAT family. Several different kinases...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.24.10.4184-4195.2004

    authors: Okamura H,Garcia-Rodriguez C,Martinson H,Qin J,Virshup DM,Rao A

    更新日期:2004-05-01 00:00:00

  • SUMOylation Regulates Growth Factor Independence 1 in Transcriptional Control and Hematopoiesis.

    abstract::Cell fate specification requires precise coordination of transcription factors and their regulators to achieve fidelity and flexibility in lineage allocation. The transcriptional repressor growth factor independence 1 (GFI1) is comprised of conserved Snail/Slug/Gfi1 (SNAG) and zinc finger motifs separated by a linker ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01001-15

    authors: Andrade D,Velinder M,Singer J,Maese L,Bareyan D,Nguyen H,Chandrasekharan MB,Lucente H,McClellan D,Jones D,Sharma S,Liu F,Engel ME

    更新日期:2016-05-02 00:00:00

  • Exploring functional redundancy in the immunoglobulin mu heavy-chain gene enhancer.

    abstract::Immunoglobulin (Ig) mu heavy-chain gene enhancer activity is mediated by multiple DNA binding proteins. Mutations of several protein binding sites in the enhancer do not affect enhancer activity significantly. This feature, termed redundancy, is thought to be due to functional compensation of the mutated sites by othe...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.18.11.6870

    authors: Dang W,Nikolajczyk BS,Sen R

    更新日期:1998-11-01 00:00:00

  • C-Terminal binding protein is a transcriptional repressor that interacts with a specific class of vertebrate Polycomb proteins.

    abstract::Polycomb (Pc) is part of a Pc group (PcG) protein complex that is involved in repression of gene activity during Drosophila and vertebrate development. To identify proteins that interact with vertebrate Pc homologs, we performed two-hybrid screens with Xenopus Pc (XPc) and human Pc 2 (HPC2). We find that the C-termina...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.19.1.777

    authors: Sewalt RG,Gunster MJ,van der Vlag J,Satijn DP,Otte AP

    更新日期:1999-01-01 00:00:00

  • Construction of an opal suppressor by oligonucleotide-directed mutagenesis of a Saccharomyces cerevisiae tRNA(Trp) gene.

    abstract::In vitro mutagenesis was used to create putative opal suppressor alleles of a tRNA(Trp) gene of Saccharomyces cerevisiae. The construct with the requisite anticodon change did not result in an active suppressor, whereas when a second change was introduced into the portion of the gene encoding the intron, an active and...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.8.4379

    authors: Atkin AL,Roy KL,Bell JB

    更新日期:1990-08-01 00:00:00

  • Activation of the STAT signaling pathway can cause expression of caspase 1 and apoptosis.

    abstract::Protein tyrosine kinases activate the STAT (signal transducer and activator of transcription) signaling pathway, which can play essential roles in cell differentiation, cell cycle control, and development. However, the potential role of the STAT signaling pathway in the induction of apoptosis remains unexplored. Here ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.9.5328

    authors: Chin YE,Kitagawa M,Kuida K,Flavell RA,Fu XY

    更新日期:1997-09-01 00:00:00

  • RAD10, an excision repair gene of Saccharomyces cerevisiae, is involved in the RAD1 pathway of mitotic recombination.

    abstract::The RAD10 gene of Saccharomyces cerevisiae is required for the incision step of excision repair of UV-damaged DNA. We show that the RAD10 gene is also required for mitotic recombination. The rad10 delta mutation lowered the rate of intrachromosomal recombination of a his3 duplication in which one his3 allele has a del...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.6.2485

    authors: Schiestl RH,Prakash S

    更新日期:1990-06-01 00:00:00

  • Chromatin decondensation and nuclear reprogramming by nucleoplasmin.

    abstract::Somatic cell nuclear cloning has repeatedly demonstrated striking reversibility of epigenetic regulation of cell differentiation. Upon injection into eggs, the donor nuclei exhibit global chromatin decondensation, which might contribute to reprogramming the nuclei by derepressing dormant genes. Decondensation of sperm...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.26.4.1259-1271.2006

    authors: Tamada H,Van Thuan N,Reed P,Nelson D,Katoku-Kikyo N,Wudel J,Wakayama T,Kikyo N

    更新日期:2006-02-01 00:00:00

  • Tumor necrosis factor alpha gene regulation: enhancement of C/EBPbeta-induced activation by c-Jun.

    abstract::Tumor necrosis factor alpha (TNF alpha) is a key regulatory cytokine whose expression is controlled by a complex set of stimuli in a variety of cell types. Previously, we found that the monocyte/macrophage-enriched nuclear transcription factor C/EBPbeta played an important role in the regulation of the TNF alpha gene ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.18.5.2815

    authors: Zagariya A,Mungre S,Lovis R,Birrer M,Ness S,Thimmapaya B,Pope R

    更新日期:1998-05-01 00:00:00

  • Induction of apoptosis by human Nbk/Bik, a BH3-containing protein that interacts with E1B 19K.

    abstract::The E1B 19-kilodalton protein (19K protein) is a potent apoptosis inhibitor and the adenovirus homolog of Bcl-2 (E. White, Genes Dev. 10:1-15, 1996). To obtain a better understanding of the biochemical mechanism by which the E1B 19K protein regulates apoptosis, proteins that interact with 19K have been identified; one...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.16.10.5857

    authors: Han J,Sabbatini P,White E

    更新日期:1996-10-01 00:00:00

  • Cdyl, a new partner of the inactive X chromosome and potential reader of H3K27me3 and H3K9me2.

    abstract::X chromosome inactivation is a remarkable example of chromosome-wide gene silencing and facultative heterochromatin formation. Numerous histone posttranslational modifications, including H3K9me2 and H3K27me3, accompany this process, although our understanding of the enzymes that lay down these marks and the factors th...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00866-13

    authors: Escamilla-Del-Arenal M,da Rocha ST,Spruijt CG,Masui O,Renaud O,Smits AH,Margueron R,Vermeulen M,Heard E

    更新日期:2013-12-01 00:00:00

  • Telomere maintenance through spatial control of telomeric proteins.

    abstract::The six human telomeric proteins TRF1, TRF2, RAP1, TIN2, POT1, and TPP1 can form a complex called the telosome/shelterin, which is required for telomere protection and length control. TPP1 has been shown to regulate both POT1 telomere localization and telosome assembly through its binding to TIN2. It remains to be det...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00603-07

    authors: Chen LY,Liu D,Songyang Z

    更新日期:2007-08-01 00:00:00

  • SIRT4 represses peroxisome proliferator-activated receptor α activity to suppress hepatic fat oxidation.

    abstract::Sirtuins are a family of protein deacetylases, deacylases, and ADP-ribosyltransferases that regulate life span, control the onset of numerous age-associated diseases, and mediate metabolic homeostasis. We have uncovered a novel role for the mitochondrial sirtuin SIRT4 in the regulation of hepatic lipid metabolism duri...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00087-13

    authors: Laurent G,de Boer VC,Finley LW,Sweeney M,Lu H,Schug TT,Cen Y,Jeong SM,Li X,Sauve AA,Haigis MC

    更新日期:2013-11-01 00:00:00

  • Eukaryotic elongation factor 1A2 cooperates with phosphatidylinositol-4 kinase III beta to stimulate production of filopodia through increased phosphatidylinositol-4,5 bisphosphate generation.

    abstract::Eukaryotic elongation factor 1 alpha 2 (eEF1A2) is a transforming gene product that is highly expressed in human tumors of the ovary, lung, and breast. eEF1A2 also stimulates actin remodeling, and the expression of this factor is sufficient to induce the formation of filopodia, long cellular processes composed of bund...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00150-08

    authors: Jeganathan S,Morrow A,Amiri A,Lee JM

    更新日期:2008-07-01 00:00:00

  • NF-Y is essential for the recruitment of RNA polymerase II and inducible transcription of several CCAAT box-containing genes.

    abstract::Osteoclast differentiation factor (ODF)/receptor activator of NF-kappaB ligand is essential for inducing the differentiation of mature osteoclasts. We find that nuclear factor Y (NF-Y) binds to the CCAAT box on the ODF promoter and regulates its basal transcriptional activity. The CCAAT box on the ODF gene is required...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.25.1.512-522.2005

    authors: Kabe Y,Yamada J,Uga H,Yamaguchi Y,Wada T,Handa H

    更新日期:2005-01-01 00:00:00