Abstract:
:A G to T mutation has been observed at the third position of codon 249 of the p53 tumor-suppressor gene in over 50% of the hepatocellular carcinoma cases associated with high exposure to aflatoxin B(1) (AFB(1)). Hypotheses have been put forth that AFB(1), in concert with hepatitis B virus (HBV), may play a role in the formation of, and/or the selection for, this mutation. The primary DNA adduct of AFB(1) is 8,9-dihydro-8-(N(7)-guanyl)-9-hydroxyaflatoxin B(1) (AFB(1)-N7-Gua), which is converted naturally to two secondary lesions, an apurinic site and an AFB(1)-formamidopyrimidine (AFB(1)-FAPY) adduct. AFB(1)-FAPY is detected at near maximal levels in rat DNA days to weeks after AFB(1) exposure, underscoring its high persistence in vivo. The present study reveals two striking properties of this DNA adduct: (i) AFB(1)-FAPY was found to cause a G to T mutation frequency in Escherichia coli approximately 6 times higher than that of AFB(1)-N7-Gua, and (ii) one proposed rotamer of AFB(1)-FAPY is a block to replication, even when the efficient bypass polymerase MucAB is used by the cell. Taken together, these characteristics make the FAPY adduct the prime candidate for both the genotoxicity of aflatoxin, because mammalian cells also have similar bypass mechanisms for combating DNA damage, and the mutagenicity that ultimately may lead to liver cancer.
journal_name
Proc Natl Acad Sci U S Aauthors
Smela ME,Hamm ML,Henderson PT,Harris CM,Harris TM,Essigmann JMdoi
10.1073/pnas.102167699keywords:
subject
Has Abstractpub_date
2002-05-14 00:00:00pages
6655-60issue
10eissn
0027-8424issn
1091-6490pii
99/10/6655journal_volume
99pub_type
杂志文章abstract::The major virulence determinant of the rodent malaria parasite, Plasmodium yoelii, has remained unresolved since the discovery of the lethal line in the 1970s. Because virulence in this parasite correlates with the ability to invade different types of erythrocytes, we evaluated the potential role of the parasite eryth...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0811313106
更新日期:2009-04-28 00:00:00
abstract::Classic physiology studies dating to the 1930s demonstrate that moderate or transient glucocorticoid (GC) exposure improves muscle performance. The ergogenic properties of GCs are further evidenced by their surreptitious use as doping agents by endurance athletes and poorly understood efficacy in Duchenne muscular dys...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1512968112
更新日期:2015-12-08 00:00:00
abstract::Previous studies have identified lipid-poor high density lipoproteins with electrophoretic pre-beta mobility as the initial acceptors of cell-derived cholesterol in human plasma. These lipoproteins contain apolipoprotein A-I (apo A-I) as their sole apolipoprotein. In the present study, incubation of human plasma with ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.5.1834
更新日期:1994-03-01 00:00:00
abstract::Cambodia, in which both Plasmodium vivax and Plasmodium falciparum are endemic, has been the focus of numerous malaria-control interventions, resulting in a marked decline in overall malaria incidence. Despite this decline, the number of P vivax cases has actually increased. To understand better the factors underlying...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1608828113
更新日期:2016-12-13 00:00:00
abstract::Tephritid fruit flies belonging to the Rhagoletis pomonella sibling species complex are controversial because they have been proposed to diverge in sympatry (in the absence of geographic isolation) by shifting and adapting to new host plants. Here, we report evidence suggesting a surprising source of genetic variation...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1730757100
更新日期:2003-09-02 00:00:00
abstract::Existing moral psychology research commonly explains certain phenomena in terms of a motivation to blame. However, this motivation is not measured directly, but rather is inferred from other measures, such as participants' judgments of an agent's blameworthiness. The present paper introduces new methods for assessing ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1501592112
更新日期:2015-03-24 00:00:00
abstract::The avian neuroretina (NR) is part of the central nervous system and is composed of photoreceptors, neuronal cells, and Müller (glial) cells. These cells are derived from proliferating neuroectodermal precursors that differentiate after terminal mitosis and become organized in cell strata. Genes that are specifically ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.88.10.4503
更新日期:1991-05-15 00:00:00
abstract::Protein synthesis initiation in reticulocyte lysates is inhibited by heme deficiency, low levels of double-stranded RNA (dsRNA), oxidized glutathione (GSSG), or the purified kinase (HRI) that acts on the alpha polypeptide of eukaryotic initiation factor 2 (eIF-2alpha). The phosphoprotein profiles produced in lysates i...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.76.5.2118
更新日期:1979-05-01 00:00:00
abstract::A lost navigator must identify its current location and recover its facing direction to restore its bearings. We tested the idea that these two tasks--place recognition and heading retrieval--might be mediated by distinct cognitive systems in mice. Previous work has shown that numerous species, including young childre...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1424194112
更新日期:2015-05-19 00:00:00
abstract::The MAK16 gene was first defined as a gene whose mutation resulted in loss of M1 double-stranded RNA virus-like particles. The mak16-1 mutation also produces temperature-sensitive cell growth. We report here that mak16-1 cells arrest at the nonpermissive temperature in G1 phase, such that they are mating competent. We...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.16.6007
更新日期:1988-08-01 00:00:00
abstract::The major auxin-binding protein in maize membranes is thought to function as a physiological receptor. From earlier information, including the use of site-directed irreversible inhibitors, several of the amino acids likely to form part of the active auxin-binding site were provisionally assigned. Inspection of the ami...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.15.7208
更新日期:1992-08-01 00:00:00
abstract::A scientist may publish tens or hundreds of papers over a career, but these contributions are not evenly spaced in time. Sixty years of studies on career productivity patterns in a variety of fields suggest an intuitive and universal pattern: Productivity tends to rise rapidly to an early peak and then gradually decli...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1702121114
更新日期:2017-10-31 00:00:00
abstract::We previously isolated from mouse spleen an octapeptide (LSPFPFDL) that in association with the class I major histocompatibility complex protein Ld is recognized by the antigen-specific receptor of an alloreactive CD8+ T-cell clone (2C). Guided by an assay dependent upon the same 2C T-cell receptor, we have now isolat...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.23.11272
更新日期:1993-12-01 00:00:00
abstract::HetR is an essential regulator of heterocyst development in cyanobacteria. Many mutations in HetR render Anabaena incapable of nitrogen fixation. The protein binds to a DNA palindrome upstream of hetP and other genes. We have determined the crystal structures of HetR complexed with palindromic DNA targets, 21, 23, and...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1305971110
更新日期:2013-05-07 00:00:00
abstract::In Drosophila, multiple isoforms of alpha-glycerol-3-phosphate dehydrogenase (sn-glycerol-3-phosphate: NAD+ 2-oxidoreductase, EC 1.1.1.8) are produced in a tissue- and stage-specific manner. To understand the underlying molecular basis of these isoforms, we have sequenced a 5.8-kilobase region of the Drosophila genome...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.13.5020
更新日期:1989-07-01 00:00:00
abstract::A photolyzable derivative of dipeptidyl-tRNA, p-azido-N-tBoc-Phe-[3H]Phe-tRNA, bound reversibly to 70S ribosomes in the presence of poly(U), becomes, when irradiated, covalently attached to components of the 50S ribosomal subunit. Most of the reaction occurs within the 23S RNA, while ribosomal proteins are only weakly...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.72.11.4332
更新日期:1975-11-01 00:00:00
abstract::The Hsp90 chaperone buffers development against a wide range of morphological changes in many organisms and in Drosophila masks the effects of hidden genetic variation. Theory predicts that genetic and nongenetic buffering will share common mechanisms. For example, it is argued that Hsp90 genetic buffering evolved sol...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1835613100
更新日期:2003-11-11 00:00:00
abstract::Oligomerization of members of the p53 family of transcription factors (p53, p63, and p73) is essential for their distinct functions in cell-cycle control and development. To elucidate the molecular basis for tetramer formation of the various family members, we solved the crystal structure of the human p73 tetramerizat...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0905867106
更新日期:2009-10-20 00:00:00
abstract::We have evaluated the effect of ligand binding on expression of the receptor for IgE on rat basophilic leukemia (RBL) cells. RBL cells were grown in the presence or absence of 131I-labeled IgE and sometimes were also surface labeled with 125I. We found that cells grown in the presence of IgE continued to accumulate re...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.82.5.1522
更新日期:1985-03-01 00:00:00
abstract::The functional capacities of CD8(+) T cells important for virus clearance are influenced by interactions with antigen presenting cells (APCs) and CD4(+) T cells during initial selection, subsequent expansion, and development of memory. Recently, investigators have shown that polyfunctional T cells correlate best with ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0915168107
更新日期:2010-02-23 00:00:00
abstract::Neuropathic pain afflicts millions of individuals and represents a major health problem for which there is limited effective and safe therapy. Emerging literature links altered sphingolipid metabolism to nociceptive processing. However, the neuropharmacology of sphingolipid signaling in the central nervous system in t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1820466116
更新日期:2019-05-21 00:00:00
abstract::Human Bestrophin 1 (hBest1) is a calcium-activated chloride channel that regulates neuronal excitability, synaptic activity, and retinal homeostasis. Mutations in hBest1 cause the autosomal-dominant Best macular dystrophy (BMD). Because hBest1 mutations cause BMD, but a knockout does not, we wondered if hBest1 mutants...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1400248111
更新日期:2014-04-29 00:00:00
abstract::DNA chip technology enables simultaneous examination of how approximately 6,200 Saccharomyces cerevisiae gene transcript levels, representing the entire genome, respond to environmental change. By using chips bearing oligonucleotide arrays, we show that, after exposure to the alkylating agent methyl methanesulfonate, ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.96.4.1486
更新日期:1999-02-16 00:00:00
abstract::The eukaryote endomembrane system contains a class of H(+)-pumping ATPase (H(+)-ATPases) of the vacuolar type (V-ATPases) that are responsible for the acidification of organelles. Their action is critical to numerous physiological processes, but the regulatory mechanisms that may control activity are not yet fully und...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.18.8547
更新日期:1994-08-30 00:00:00
abstract::Neurons vary in their capacity to produce, store, and release neuropeptides packaged in dense-core vesicles (DCVs). Specifically, neurons used for cotransmission have terminals that contain few DCVs and many small synaptic vesicles, whereas neuroendocrine neuron terminals contain many DCVs. Although the mechanistic ba...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1322170111
更新日期:2014-03-04 00:00:00
abstract::We describe a cell-free system in which the transcription of the yeast metallothionein gene is inducible by the addition of metal ions plus a specific regulatory protein. Efficient transcription requires the complete yeast ACE1 metalloregulatory protein, including both its DNA-binding and transactivation domains; a mo...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.21.8377
更新日期:1989-11-01 00:00:00
abstract::To evade their predators, animals must quickly detect potential threats, gauge risk, and mount a response. Putative neural circuits responsible for these tasks have been isolated in laboratory studies. However, it is unclear whether and how these circuits combine to generate the flexible, dynamic sequences of evasion ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1809140115
更新日期:2018-11-27 00:00:00
abstract::Overlapping cDNAs derived from the chicken alpha-fibrinogen mRNA have been sequenced, beginning from within the coding region for the signal peptide of this subunit and terminating within the poly(A) extension. The predicted size of chicken alpha-fibrinogen is 54,187 daltons, which is the smallest of any alpha chain r...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.87.13.5198
更新日期:1990-07-01 00:00:00
abstract::Surgical removal of one or both atrial appendages was employed in rats to reduce the intrinsic stores of atriopeptin (AP). In conscious rats (with intact baroreceptor reflexes), bilateral or unilateral atrial appendectomy suppressed the diuresis and natriuresis produced by acute volume expansion. Surprisingly, volume ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.9.3155
更新日期:1988-05-01 00:00:00
abstract::High-affinity ligands of the reverse transcriptase of human immunodeficiency virus type 1 (HIV-1) were isolated by the SELEX procedure (systematic evolution of ligands by exponential enrichment) from RNA populations randomized at 32 positions. Analysis of these ligands revealed a pseudoknot consensus with primary sequ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.15.6988
更新日期:1992-08-01 00:00:00