Abstract：
:Much is known about the distal DNA damage repair response. In particular, many of the enzymes and auxiliary proteins that participate in DNA repair have been characterized. In addition, knowledge of signaling pathways activated in response to DNA damage is increasing. In contrast, comparatively less is known of DNA damage-sensing molecules or of the specific alterations to chromatin structure recognized by such DNA damage sensors. Thus, precisely how chromatin structure is altered in response to DNA damage and how such alterations regulate DNA repair processes remain important unanswered questions. In vertebrates, phosphorylation of the histone variant H2A.X occurs rapidly after double-strand break formation, extends over megabase chromatin domains, and is required for stable accumulation of repair proteins at damage foci. We have shown that reactive oxygen species (ROS)-induced DNA single-strand breaks induce the incorporation of 32P specifically into histone H3. ADP-Ribosylation of histones may stimulate local chromatin relaxation to facilitate the repair process, and, indeed, histone ribosylation preceded DNA damage-induced histone H3 phosphorylation. However, H3 phosphorylation occurred concomitant with overall chromatin condensation, as revealed by decreased sensitivity of chromatin to digestion by micrococcal nuclease and by DAPI staining of nuclei. Inhibitors of the ERK and p38MAPK pathways and inhibition of poly(ADP-ribose) polymerase all reduced ROS-induced H3 phosphorylation, chromatin condensation, and cell death. Precisely how changes in the post-translational modification of histone H3 regulate the survival response remains unclear. Attempts to determine the precise site of histone H3 phosphorylation, putative histone H3 kinases, and histone H3 interacting proteins are underway.
journal_name
Drug Metab Revjournal_title
Drug metabolism reviewsauthors
Monks TJ,Xie R,Tikoo K,Lau SSdoi
10.1080/03602530600959649subject
Has Abstractpub_date
2006-01-01 00:00:00pages
755-67issue
4eissn
0360-2532issn
1097-9883pii
RR1270M733784484journal_volume
38pub_type
杂志文章,评审abstract：:The cannabinoid receptor 1 (CB1) is a G protein-coupled receptor (GPCR) that is located primarily in the central nervous system. CB1 is a therapeutic target which may impact pathways to mediate pain, neurodegenerative disorders, hunger, and drug-seeking behavior. Despite these benefits, development of orthosteric ther...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602532.2018.1428342
更新日期：2018-02-01 00:00:00
abstract：:For patients undergoing cardiopulmonary bypass (CPB) during cardiac surgery, there are well-documented changes in the pharmacokinetics (PK) of commonly administered drugs. Although multiple factors potentially underpin these changes, there has been scant research attention on the impact of CPB to alter the activities ...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602532.2017.1417423
更新日期：2018-05-01 00:00:00
abstract：:Glycyrrhizic acid is widely applied as a sweetener in food products and chewing tobacco. In addition, it is of clinical interest for possible treatment of chronic hepatitis C. In some highly exposed subjects, side effects such as hypertension and symptoms associated with electrolyte disturbances have been reported. To...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1081/dmr-100104400
更新日期：2001-05-01 00:00:00
abstract：:Bioconjugation of therapeutic agents has been used as a selective drug delivery platform for many therapeutic areas. Bioconjugates are prepared by the covalent linkage of active compounds (small or large molecule) to a carrier molecule (lipids, proteins, peptides, carbohydrates, and polymers) through a chemical linker...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602532.2020.1716784
更新日期：2020-02-01 00:00:00
abstract：:Monkeys, especially macaques, including cynomolgus (Macaca fascicularis) and rhesus monkeys (Macaca mulatta), are frequently used in drug metabolism studies due to their evolutionary closeness to humans. Recently, numerous cytochrome P450 (P450 or CYP) cDNAs have been identified and characterized in cynomolgus and rhe...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602532.2010.549492
更新日期：2011-08-01 00:00:00
abstract：:1. The metabolic activity of the gastrointestinal microflora can be modified by numerous factors derived from the host, the host's environment, and the flora itself. 2. Marked differences exist in microbial composition and metabolism of the gut floras of different species of animal, and in the degree of colonization o...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602538808994135
更新日期：1988-01-01 00:00:00
abstract：:Human CYP1A2 is one of the major CYPs in human liver and metabolizes a number of clinical drugs (e.g., clozapine, tacrine, tizanidine, and theophylline; n > 110), a number of procarcinogens (e.g., benzo[a]pyrene and aromatic amines), and several important endogenous compounds (e.g., steroids). CYP1A2 is subject to rev...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602530903286476
更新日期：2010-05-01 00:00:00
abstract：:Enormous efforts toward predicting the metabolic fate of a drug have been driven by the high attrition rate in drug development. To accelerate such efforts, it is critical to elucidate the molecular mechanisms of drug recognition by drug-metabolizing enzymes. Therefore, it is not surprising that an increasing number o...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602532.2011.645581
更新日期：2012-02-01 00:00:00
abstract：:Bupropion is an atypical antidepressant of the aminoketone group, structurally related to cathinone, associated with a wide interindividual variability. An extensive pharmacokinetic and pharmacodynamic review of bupropion was performed, also focusing on chemical, pharmacological, toxicological, clinical and forensic a...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602532.2019.1620763
更新日期：2019-08-01 00:00:00
abstract：:Pregnane X receptor (PXR) and constitutive active/androstane receptor (CAR), members of the nuclear receptor superfamily, are two major xeno-sensing transcription factors. They can be activated by a broad range of lipophilic xenobiotics including therapeutics drugs. In addition to xenobiotics, endogenous compounds suc...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602532.2013.835630
更新日期：2013-11-01 00:00:00
abstract：:Like any other drugs, antiallergic medications can be associated with large inter- and intraindividual variability in their disposition. The best-documented examples belong to the H1 antihistamines. Variable drugs are more likely to show unpredictable therapeutic response with both increased risks of side effects and ...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/10837450902891485
更新日期：2009-01-01 00:00:00
abstract：:At present, the methods and enzymology of the UDP-glucuronosyltransferases (UGTs) lag behind that of the cytochromes P450 (CYPs). About 15 human UGTs have been identified, and knowledge about their regulation, substrate selectivity, and tissue distribution has progressed recently. Alamethicin has been characterized as...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1081/dmr-120000653
更新日期：2001-08-01 00:00:00
abstract：:N-acetyltransferase 1 (NAT1), a polymorphic Phase II enzyme, plays an essential role in metabolizing heterocyclic and aromatic amines, which are implicated in urinary bladder cancer (BCa). This systematic review investigates a possible association between the different NAT1 genetic polymorphisms and BCa risk. Medline,...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,meta分析,评审
doi：10.1080/03602532.2017.1415928
更新日期：2018-05-01 00:00:00
abstract：:In this paper, we evaluate methodologies and null mouse models used to study drug transporter function in vitro and in vivo. P-glycoprotein and MRP null mice have been used to examine many aspects of xenobiotic distribution and bioavailability. Their advantage over conventional models is that they allow the exclusion ...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602530802605040
更新日期：2009-01-01 00:00:00
abstract：:The CYP4 family of cytochrome P450 enzymes and the mammalian peroxidases covalently bind their heme groups. In the CYP4 enzymes this involves one, and in the peroxidases two, covalent ester links between heme methys and carboxylic acid side-chains. In addition, in myeloperoxidase, a methionine forms a sulfonium link t...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602530802186439
更新日期：2008-01-01 00:00:00
abstract：:The rat P450IIA subfamily was characterized at the protein, cDNA, and gene level. The purified IIA1 and IIA2 P-450s displayed distinct positional specificities toward hydroxylation of the prototype substrate testosterone. The IIA1 and IIA2 genes were also regulated differently during development; IIA1 was expressed wi...
journal_title：Drug metabolism reviews
pub_type： 杂志文章
doi：10.3109/03602538909103582
更新日期：1989-01-01 00:00:00
abstract：:Human tumors arise from multiple genetic changes that gradually transform growth-limited cells into highly invasive cells that are unresponsive to growth controls. The genetic evolution of normal cells into cancer cells is largely determined by the fidelity of DNA replication, repair, and division. Cell-cycle arrest i...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1081/dmr-100102335
更新日期：2000-08-01 00:00:00
abstract：:The Pharmacogenetics and Pharmacogenomics Knowledge Base (PharmGKB: http://www.pharmgkb.org) is devoted to disseminating primary data and knowledge in pharmacogenetics and pharmacogenomics. We are annotating the genes that are most important for drug response and present this information in the form of Very Important ...
journal_title：Drug metabolism reviews
pub_type： 杂志文章
doi：10.1080/03602530802413338
更新日期：2008-01-01 00:00:00
abstract：:The efficacy of drugs has to be demonstrated following the principal approach of statistical evaluation in controlled clinical trials. This scientifically and internationally accepted numerical approach has developed over the years to its importance, in contrast to the more pharmacologically attempt to extrapolate hum...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1081/dmr-200033500
更新日期：2004-10-01 00:00:00
abstract：:In this case study, in vitro and in vivo data were provided for saquinavir (SQV) showing that drug transporters play a significant role in the absorption and disposition of drugs. This article is focused on the more practical points with a technical emphasis. Currently many in vitro and in vivo experimental models hav...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1081/dmr-120037570
更新日期：2004-05-01 00:00:00
abstract：:Hormone-dependent breast cancers that overexpress the ligand-binding nuclear transcription factor, estrogen receptor (ER), represent the most common form of breast epithelial malignancy. Exposure of breast epithelial cells to a redox-cycling and arylating quinone induces mitogen-activated protein kinase phosphorylatio...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602530600959391
更新日期：2006-01-01 00:00:00
abstract：:Numerous experimental and epidemiological studies have demonstrated that polycyclic aromatic hydrocarbons (PAHs), which are major constituents of cigarette tobacco tar, are strongly involved in the pathogenesis of the cardiovascular diseases (CVDs). Knowing that PAH-induced toxicities are mediated by the activation of...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602530600632063
更新日期：2006-01-01 00:00:00
abstract：:An association between marijuana use and schizophrenia has been noted for decades, and the recent emergence of high-efficacy synthetic cannabinoids (SCBs) as drugs of abuse has lead to a growing number of clinical reports of persistent psychotic effects in users of these substances. The mechanisms underlying SCB-elici...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602532.2018.1428343
更新日期：2018-02-01 00:00:00
abstract：:S-carboxymethyl-L-cysteine, the side-chain carboxymethyl derivative of the sulfur-containing amino acid, cysteine, has been known and available for almost 80 years. During this time, it has been put to a variety of uses, but it is within the field of respiratory medicine that, presently, it has found a clinical niche....
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602532.2011.631015
更新日期：2012-05-01 00:00:00
abstract：:This article reviews the regulatory, social, policy, and other issues that will shape the development of pharmacogenomics applications. We identify and analyze 19 key public policy issues, ranging from the economic incentives for linked diagnostic-drug development, to the regulation of tests and drugs, and to privacy ...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602530801952500
更新日期：2008-01-01 00:00:00
abstract：:Population pharmacokinetics describe the typical relationships between physiology (both normal and disease altered) and pharmacokinetics, the interindividual variability in these relationships, and their residual intraindividual variability. Knowledge of population kinetics can help one to choose initial drug dosage, ...
journal_title：Drug metabolism reviews
pub_type： 杂志文章
doi：10.3109/03602538409015063
更新日期：1984-01-01 00:00:00
abstract：:Voriconazole, a second-generation triazole frequently used for the prophylaxis and treatment of invasive fungal infections, undergoes complex metabolism mainly involving various (polymorphic) cytochrome P450 enzymes in humans. Although high inter- and intraindividual variability in voriconazole pharmacokinetics have b...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602532.2019.1632888
更新日期：2019-08-01 00:00:00
abstract：:The reabsorptive and excretory capacity of the kidney has an important influence on the systemic concentration of drugs. Multidrug resistance proteins (MRP/ABCC) expressed in the kidney play a critical role in the tubular efflux of a wide variety of drugs and toxicants, and, in particular, of their negatively charged ...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602530500205275
更新日期：2005-01-01 00:00:00
abstract：:In summary, we have shown that steroid D-ring, but not steroid A-ring, glucuronide conjugates act at the level of the bile canaliculus to decrease bile-acid-dependent flow, initially; and subsequently, bile-acid-independent flow. These data indicate that glucuronide conjugates are not necessarily inactive; the present...
journal_title：Drug metabolism reviews
pub_type： 杂志文章
doi：10.3109/03602538308991419
更新日期：1983-01-01 00:00:00
abstract：:The body is considered as a system composed of a number of subsystems. The response(s) of a drug is a complicated function of the concentration in the blood plasma, which in turn is some function of the dosage input. The dose-response curve of a drug in a subsystem (e.g., isolated organ) is, over a limited concentrati...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602538409015072
更新日期：1984-01-01 00:00:00
