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Article ; Online: Automated High-Throughput Flow Cytometry for High-Content Screening in Antibody Development.

Wang, Yana / Yoshihara, Tomoki / King, Samson / Le, Tinh / Leroy, Patrick / Zhao, Xiansi / Chan, Ching Kit / Yan, Zhong-Hua / Menon, Saurabh

SLAS discovery : advancing life sciences R & D

2018 Volume 23, Issue 7, Page(s) 656–666

Abstract: The tedious sample preparation for flow cytometry limits the throughput and thus its usage as a primary screening method despite its sensitivity and accuracy. With the growing focus on utilizing antibodies as a therapeutic modality in drug discovery, it ... ...

Abstract	The tedious sample preparation for flow cytometry limits the throughput and thus its usage as a primary screening method despite its sensitivity and accuracy. With the growing focus on utilizing antibodies as a therapeutic modality in drug discovery, it is critical to develop a high-throughput flow cytometry (HTFC) workflow to cope with the increasing need to support antibody discovery programs. We have developed a seamless HTFC sample preparation and readout workflow using the HighRes modular robotic system and the IntelliCyt iQue Screener PLUS. To fully utilize the advantages offered by flow cytometry, we typically multiplex multiple cell lines of interest in one well to simultaneously quantitate on-target activity and nonspecific activity along with measurement of antibody concentration. The ability to measure multiple parameters coupled with speed and increased accuracy provides gains in productivity and helps speed up antibody lead discovery.
MeSH term(s)	Animals ; Antibodies, Monoclonal/pharmacology ; Automation ; Drug Discovery/methods ; Drug Evaluation, Preclinical ; Flow Cytometry/methods ; High-Throughput Screening Assays/methods ; Humans ; Hybridomas ; Immunoglobulin G/pharmacology ; Mice ; Workflow
Chemical Substances	Antibodies, Monoclonal ; Immunoglobulin G
Language	English
Publishing date	2018-06-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	2885123-7
ISSN	2472-5560 ; 2472-5552
ISSN (online)	2472-5560
ISSN	2472-5552
DOI	10.1177/2472555218776607
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Article ; Online: Antibody-free detection of cellular neddylation dynamics of Cullin1.

Schwinn, Marie K / Hoang, Trish / Yang, Xiaofeng / Zhao, Xiansi / Ma, Jingya / Li, Ping / Wood, Keith V / Mallender, William D / Bembenek, Michael E / Yan, Zhong-Hua

Analytical biochemistry

2018 Volume 555, Page(s) 67–72

Abstract: Neddylation is a posttranslational modification that regulates protein stability, activity, and subcellular localization. Here, we describe a new tool for exploring the neddylation cycle of cullin1 (Cul1) directly in a cellular context. This assay ... ...

Abstract	Neddylation is a posttranslational modification that regulates protein stability, activity, and subcellular localization. Here, we describe a new tool for exploring the neddylation cycle of cullin1 (Cul1) directly in a cellular context. This assay utilizes the NanoLuc
MeSH term(s)	Biological Assay/methods ; Cullin Proteins/genetics ; Cullin Proteins/metabolism ; HCT116 Cells ; HEK293 Cells ; Humans ; NEDD8 Protein/genetics ; NEDD8 Protein/metabolism ; Protein Processing, Post-Translational
Chemical Substances	Cullin 1 ; Cullin Proteins ; NEDD8 Protein ; NEDD8 protein, human
Language	English
Publishing date	2018-05-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	1110-1
ISSN	1096-0309 ; 0003-2697
ISSN (online)	1096-0309
ISSN	0003-2697
DOI	10.1016/j.ab.2018.05.002
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Article ; Online: Impact of guanidine-containing backbone linkages on stereopure antisense oligonucleotides in the CNS.

Kandasamy, Pachamuthu / Liu, Yuanjing / Aduda, Vincent / Akare, Sandheep / Alam, Rowshon / Andreucci, Amy / Boulay, David / Bowman, Keith / Byrne, Michael / Cannon, Megan / Chivatakarn, Onanong / Shelke, Juili Dilip / Iwamoto, Naoki / Kawamoto, Tomomi / Kumarasamy, Jayakanthan / Lamore, Sarah / Lemaitre, Muriel / Lin, Xuena / Longo, Kenneth /

Looby, Richard / Marappan, Subramanian / Metterville, Jake / Mohapatra, Susovan / Newman, Bridget / Paik, Ik-Hyeon / Patil, Saurabh / Purcell-Estabrook, Erin / Shimizu, Mamoru / Shum, Pochi / Standley, Stephany / Taborn, Kris / Tripathi, Snehlata / Yang, Hailin / Yin, Yuan / Zhao, Xiansi / Dale, Elena / Vargeese, Chandra

Nucleic acids research

2022 Volume 50, Issue 10, Page(s) 5401–5423

Abstract: Attaining sufficient tissue exposure at the site of action to achieve the desired pharmacodynamic effect on a target is an important determinant for any drug discovery program, and this can be particularly challenging for oligonucleotides in deep tissues ...

Abstract	Attaining sufficient tissue exposure at the site of action to achieve the desired pharmacodynamic effect on a target is an important determinant for any drug discovery program, and this can be particularly challenging for oligonucleotides in deep tissues of the CNS. Herein, we report the synthesis and impact of stereopure phosphoryl guanidine-containing backbone linkages (PN linkages) to oligonucleotides acting through an RNase H-mediated mechanism, using Malat1 and C9orf72 as benchmarks. We found that the incorporation of various types of PN linkages to a stereopure oligonucleotide backbone can increase potency of silencing in cultured neurons under free-uptake conditions 10-fold compared with similarly modified stereopure phosphorothioate (PS) and phosphodiester (PO)-based molecules. One of these backbone types, called PN-1, also yielded profound silencing benefits throughout the mouse brain and spinal cord at low doses, improving both the potency and durability of response, especially in difficult to reach brain tissues. Given these benefits in preclinical models, the incorporation of PN linkages into stereopure oligonucleotides with chimeric backbone modifications has the potential to render regions of the brain beyond the spinal cord more accessible to oligonucleotides and, consequently, may also expand the scope of neurological indications amenable to oligonucleotide therapeutics.
MeSH term(s)	Animals ; Cells, Cultured ; Central Nervous System ; Guanidine/chemistry ; Mice ; Neurons/drug effects ; Oligonucleotides, Antisense/chemistry ; Oligonucleotides, Antisense/pharmacology ; Phosphorothioate Oligonucleotides ; Ribonuclease H/metabolism
Chemical Substances	Oligonucleotides, Antisense ; Phosphorothioate Oligonucleotides ; Ribonuclease H (EC 3.1.26.4) ; Guanidine (JU58VJ6Y3B)
Language	English
Publishing date	2022-01-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkac037
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Zs.A 1067: Show issues

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Article: Antibody-free detection of cellular neddylation dynamics of Cullin1

Schwinn, Marie K / Jingya Ma / Keith V. Wood / Michael E. Bembenek / Ping Li / Trish Hoang / William D. Mallender / Xiansi Zhao / Xiaofeng Yang / Zhong-Hua Yan

Analytical biochemistry. 2018 Aug. 15, v. 555

2018

Abstract	Neddylation is a posttranslational modification that regulates protein stability, activity, and subcellular localization. Here, we describe a new tool for exploring the neddylation cycle of cullin1 (Cul1) directly in a cellular context. This assay utilizes the NanoLuc® Binary Technology (NanoBiT) to monitor the covalent neddylation status of Cul1. A stable clonal cell line derived from HEK293 was developed that expressed a C-terminus LgBiT tagged-Cul1 and N-terminus SmBiT tagged-Nedd8. Using this cell line, we screened inhibitors that are known to disrupt Nedd8 biology and demonstrated that both inhibitors of Nedd8-activating enzyme (NAE) and Constitutive photomorphogenesis 9 signalosome (CSN) complex produce concentration and time dependent signal decreases and increases, respectively. The kinetics of both responses could be monitored in real time and demonstrated that modulation of the Nedd8 pathway occurs rapidly. Further characterization of the cellular components of this cell line was performed in order to quantify the various levels of Cul1, Nedd8 and NAE and determined to be near endogenous levels. There was no difference between control and stably transfected cell lines in viability studies of NAE and CSN inhibitors. Taken together, these results suggest that the NanoBiT assay can be used to monitor Cul1 neddylation specifically and in real time.
Keywords	cell lines ; constitutive photomorphogenesis 9 signalosome ; post-translational modification ; viability
Language	English
Dates of publication	2018-0815
Size	p. 67-72.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	1110-1
ISSN	1096-0309 ; 0003-2697
ISSN (online)	1096-0309
ISSN	0003-2697
DOI	10.1016/j.ab.2018.05.002
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Control of backbone chemistry and chirality boost oligonucleotide splice switching activity.

Kandasamy, Pachamuthu / McClorey, Graham / Shimizu, Mamoru / Kothari, Nayantara / Alam, Rowshon / Iwamoto, Naoki / Kumarasamy, Jayakanthan / Bommineni, Gopal R / Bezigian, Adam / Chivatakarn, Onanong / Butler, David C D / Byrne, Michael / Chwalenia, Katarzyna / Davies, Kay E / Desai, Jigar / Shelke, Juili Dilip / Durbin, Ann F / Ellerington, Ruth / Edwards, Ben /

Nucleic acids research

2022 Volume 50, Issue 10, Page(s) 5443–5466

Abstract: Although recent regulatory approval of splice-switching oligonucleotides (SSOs) for the treatment of neuromuscular disease such as Duchenne muscular dystrophy has been an advance for the splice-switching field, current SSO chemistries have shown limited ... ...

Abstract	Although recent regulatory approval of splice-switching oligonucleotides (SSOs) for the treatment of neuromuscular disease such as Duchenne muscular dystrophy has been an advance for the splice-switching field, current SSO chemistries have shown limited clinical benefit due to poor pharmacology. To overcome limitations of existing technologies, we engineered chimeric stereopure oligonucleotides with phosphorothioate (PS) and phosphoryl guanidine-containing (PN) backbones. We demonstrate that these chimeric stereopure oligonucleotides have markedly improved pharmacology and efficacy compared with PS-modified oligonucleotides, preventing premature death and improving median survival from 49 days to at least 280 days in a dystrophic mouse model with an aggressive phenotype. These data demonstrate that chemical optimization alone can profoundly impact oligonucleotide pharmacology and highlight the potential for continued innovation around the oligonucleotide backbone. More specifically, we conclude that chimeric stereopure oligonucleotides are a promising splice-switching modality with potential for the treatment of neuromuscular and other genetic diseases impacting difficult to reach tissues such as the skeletal muscle and heart.
MeSH term(s)	Animals ; Exons ; Mice ; Muscle, Skeletal ; Muscular Dystrophy, Duchenne/drug therapy ; Muscular Dystrophy, Duchenne/therapy ; Oligonucleotides, Antisense/chemistry ; Oligonucleotides, Antisense/genetics ; Oligonucleotides, Antisense/pharmacology ; Phosphorothioate Oligonucleotides/chemistry ; Phosphorothioate Oligonucleotides/pharmacology ; RNA Splicing/drug effects
Chemical Substances	Oligonucleotides, Antisense ; Phosphorothioate Oligonucleotides
Language	English
Publishing date	2022-01-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkac018
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Zs.A 1067: Show issues

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Article: The apoptotic action of the retinoid CD437/AHPN: diverse effects, common basis.

Zhao, Xiansi / Spanjaard, Remco A

Journal of biomedical science

2003 Volume 10, Issue 1, Page(s) 44–49

Abstract: Retinoids, such as all-TRANS-retinoic acid (RA), have found applications in several different types of (cancer) therapies. The synthetic retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437 or AHPN), an RA receptor (RAR)gamma ...

Abstract	Retinoids, such as all-TRANS-retinoic acid (RA), have found applications in several different types of (cancer) therapies. The synthetic retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437 or AHPN), an RA receptor (RAR)gamma agonist, not only induces RARgamma-dependent differentiation, but in contrast to RA, it also induces RARgamma-independent apoptosis in many tumor cells. This observation makes this and similar new retinoids very interesting from a clinical perspective. Several genes have been associated with CD437/AHPN-mediated apoptosis, but the multiple activities of this compound and the apparent cell-type-specific responses to treatment have made it difficult to discern a common biochemical basis for the mechanism of its apoptotic action. In this brief review, we present a model which links all CD437/AHPN-associated apoptotic effects. CD437/AHPN rapidly induces DNA adduct formation through an as-yet unknown reaction which is independent of cell type. This is followed by a cell-type-specific, largely p53-independent DNA damage response which can result in engagement of multiple cell death pathways and activation of caspases as a common endpoint. At the same time, the RARgamma-dependent pathway leads to regulation of differentiation-associated, cell-type-specific genes. CD437/AHPN, with its simultaneous differentiation and apoptosis-inducing activities, is a good prototype for new drugs which may be clinically more efficacious than those with a single activity.
MeSH term(s)	Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Cell Differentiation/drug effects ; Cell Differentiation/genetics ; DNA Adducts ; DNA Damage/drug effects ; Gene Expression Regulation/drug effects ; Humans ; Retinoids/metabolism ; Retinoids/pharmacology ; Signal Transduction/drug effects
Chemical Substances	Antineoplastic Agents ; CD 437 ; DNA Adducts ; Retinoids
Language	English
Publishing date	2003-01-06
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	1193378-1
ISSN	1423-0127 ; 1021-7770
ISSN (online)	1423-0127
ISSN	1021-7770
DOI	10.1007/bf02255996
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 4037: Show issues

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Article ; Online: Regulation of MITF stability by the USP13 deubiquitinase.

Zhao, Xiansi / Fiske, Brian / Kawakami, Akinori / Li, Juying / Fisher, David E

Nature communications

2011 Volume 2, Page(s) 414

Abstract: The microphthalmia-associated transcription factor (MITF) is essential for melanocyte development. Mutation-induced MAPK pathway activation is common in melanoma and induces MITF phosphorylation, ubiquitination, and proteolysis. Little is known about the ...

Abstract	The microphthalmia-associated transcription factor (MITF) is essential for melanocyte development. Mutation-induced MAPK pathway activation is common in melanoma and induces MITF phosphorylation, ubiquitination, and proteolysis. Little is known about the enzymes involved in MITF ubiquitination/deubiquitination. Here we report the identification of a deubiquitinating enzyme, named ubiquitin-specific protease 13 (USP13) that appears to be responsible for MITF deubiquitination, utilizing a short hairpin RNA library against known deubiquitinating enzymes. Through deubiquitination, USP13 stabilizes and upregulates MITF protein levels. Conversely, suppression of USP13 (through knockdown) leads to dramatic loss of MITF protein, but not messenger RNA. Through its effects on MITF deubiquitination, USP13 was observed to modulate expression of MITF downstream target genes and, thereby, to be essential for melanoma growth in soft agar and in nude mice. These observations suggest that as a potentially drugable protease, USP13 might be a viable therapeutic target for melanoma.
MeSH term(s)	Cell Line, Tumor ; Endopeptidases/genetics ; Endopeptidases/metabolism ; Humans ; Melanoma/enzymology ; Melanoma/genetics ; Melanoma/metabolism ; Microphthalmia-Associated Transcription Factor/chemistry ; Microphthalmia-Associated Transcription Factor/genetics ; Microphthalmia-Associated Transcription Factor/metabolism ; Ubiquitination ; Up-Regulation
Chemical Substances	MITF protein, human ; Microphthalmia-Associated Transcription Factor ; Endopeptidases (EC 3.4.-) ; USP13 protein, human (EC 3.4.19.12)
Language	English
Publishing date	2011-08-02
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/ncomms1421
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Article ; Online: Target Validation and Identification of Novel Boronate Inhibitors of the Plasmodium falciparum Proteasome.

Journal of medicinal chemistry

2018 Volume 61, Issue 22, Page(s) 10053–10066

Abstract: The Plasmodium proteasome represents a potential antimalarial drug target for compounds with activity against multiple life cycle stages. We screened a library of human proteasome inhibitors (peptidyl boronic acids) and compared activities against ... ...

Abstract	The Plasmodium proteasome represents a potential antimalarial drug target for compounds with activity against multiple life cycle stages. We screened a library of human proteasome inhibitors (peptidyl boronic acids) and compared activities against purified P. falciparum and human 20S proteasomes. We chose four hits that potently inhibit parasite growth and show a range of selectivities for inhibition of the growth of P. falciparum compared with human cell lines. P. falciparum was selected for resistance in vitro to the clinically used proteasome inhibitor, bortezomib, and whole genome sequencing was applied to identify mutations in the proteasome β5 subunit. Active site profiling revealed inhibitor features that enable retention of potent activity against the bortezomib-resistant line. Substrate profiling reveals P. falciparum 20S proteasome active site preferences that will inform attempts to design more selective inhibitors. This work provides a starting point for the identification of antimalarial drug leads that selectively target the P. falciparum proteasome.
MeSH term(s)	Amino Acid Sequence ; Animals ; Boronic Acids/chemistry ; Boronic Acids/pharmacology ; Catalytic Domain ; Cell Line ; Drug Design ; Drug Evaluation, Preclinical ; Drug Resistance/drug effects ; Humans ; Models, Molecular ; Plasmodium falciparum/enzymology ; Proteasome Endopeptidase Complex/chemistry ; Proteasome Endopeptidase Complex/metabolism ; Proteasome Inhibitors/chemistry ; Proteasome Inhibitors/pharmacology
Chemical Substances	Boronic Acids ; Proteasome Inhibitors ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
Language	English
Publishing date	2018-11-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218133-2
ISSN	1520-4804 ; 0022-2623
ISSN (online)	1520-4804
ISSN	0022-2623
DOI	10.1021/acs.jmedchem.8b01161
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Zs.B 151: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Mechanism of regulation and suppression of melanoma invasiveness by novel retinoic acid receptor-gamma target gene carbohydrate sulfotransferase 10.

Zhao, Xiansi / Graves, Carole / Ames, Sarah J / Fisher, David E / Spanjaard, Remco A

Cancer research

2009 Volume 69, Issue 12, Page(s) 5218–5225

Abstract: Retinoic acid (RA) induces growth arrest and differentiation of S91 murine melanoma cells and serves as a valuable model for this disease. RA acts through activation of RA receptors (RAR), which are members of the nuclear receptor superfamily of ligand- ... ...

Abstract	Retinoic acid (RA) induces growth arrest and differentiation of S91 murine melanoma cells and serves as a valuable model for this disease. RA acts through activation of RA receptors (RAR), which are members of the nuclear receptor superfamily of ligand-inducible transcription factors. Interestingly, differentiation is mediated by RARgamma, but not by RARalpha or RARbeta, suggesting that RARgamma possesses unique and uncharacterized molecular properties. To address this question, DNA microarrays in combination with RAR isoform-specific agonists were employed to identify novel RARgamma target genes that may play a role in this process. Here, we identified and validated carbohydrate sulfotransferase 10 (CHST10) as a novel RARgamma target gene in S91 cells. The RARgamma-inducible CHST10 promoter was obtained, and two atypical, independently functioning RA response elements were identified in a 425 bp region. Surprisingly, this fragment is bound by RARgamma, but not by RARalpha or RARbeta, thus providing a mechanism for the observed RARgamma-specific regulation. CHST10 is a sulfotransferase that forms HNK-1 glycan on neural cell adhesion proteins and glycolipids, and HNK-1 is thought to modulate cell adhesion and possibly metastasis. We show that CHST10 is also regulated by RARgamma in a significant subset of human melanoma cells, and three-dimensional cell culture migration assays suggest that CHST10 functions as a suppressor of invasiveness, but not proliferation, in these cells. Induction of CHST10 by RARgamma-activating retinoids may present a novel therapeutic strategy to inhibit invasiveness in a subset of melanoma patients.
MeSH term(s)	Base Sequence ; Cell Line, Tumor ; Chromatin Immunoprecipitation ; DNA ; Humans ; Melanoma/enzymology ; Melanoma/genetics ; Melanoma/pathology ; Molecular Sequence Data ; Neoplasm Invasiveness ; Promoter Regions, Genetic ; Receptors, Retinoic Acid/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Sulfotransferases/genetics ; Sulfotransferases/metabolism ; Retinoic Acid Receptor gamma
Chemical Substances	Receptors, Retinoic Acid ; DNA (9007-49-2) ; CHST10 protein, human (EC 2.8.2.-) ; Sulfotransferases (EC 2.8.2.-)
Language	English
Publishing date	2009-05-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-09-0705
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Article: The carcinogenic potential of extractable organic matter from urban airborne particles in Shanghai, China.

Zhao, Xiansi / Wan, Zhi / Zhu, Huigang / Chen, Renping

Mutation research

2003 Volume 540, Issue 1, Page(s) 107–117

Abstract: The genotoxicity of extractable organic matter (EOM) from airborne particles in Shanghai has been determined using short-term bioassays. EOM samples were investigated using cell morphological transformation and two-stage model of mouse skin ... ...

Abstract	The genotoxicity of extractable organic matter (EOM) from airborne particles in Shanghai has been determined using short-term bioassays. EOM samples were investigated using cell morphological transformation and two-stage model of mouse skin tumorigenicity assays to detect their carcinogenic activity. DNA adducts were detected using the 32P-postlabeling technique. The results showed that EOMs induced cell morphological transformation and played a role in tumor-initiating carcinogenesis. The EOMs of airborne particles from different districts of Shanghai had similar carcinogenic activity except the result of sample E (at downtown of Shanghai) was relatively high. The polycyclic aromatic hydrocarbon (PAH) fraction makes a major contribution to carcinogenic activity according to the results of cell morphological transformation assay. DNA adducts were also detected in skin, liver, and kidney of mouse after treatment with EOMs. It is suggested that the urban airborne particles in Shanghai, which show carcinogenic potential and genotoxic activity in our bioassays, may be responsible for the increased incidence of lung cancer in Shanghai in last few years.
MeSH term(s)	3T3 Cells/drug effects ; Air Pollutants/toxicity ; Air Pollution ; Animals ; Biotransformation ; Carcinogens/administration & dosage ; Carcinogens/adverse effects ; Cell Survival ; China ; Cricetinae ; DNA Adducts ; Female ; Fibroblasts/drug effects ; Male ; Mesocricetus/embryology ; Mice ; Mice, Inbred BALB C ; Mutagenicity Tests ; Mutagens ; Neoplasms, Experimental/metabolism ; Neoplasms, Experimental/pathology ; Occupational Exposure ; Organic Chemicals/chemistry ; Organic Chemicals/toxicity ; Phosphorus Radioisotopes ; Polycyclic Compounds/adverse effects ; Skin Neoplasms/metabolism ; Skin Neoplasms/pathology ; Tetradecanoylphorbol Acetate/administration & dosage ; Tetradecanoylphorbol Acetate/adverse effects
Chemical Substances	Air Pollutants ; Carcinogens ; DNA Adducts ; Mutagens ; Organic Chemicals ; Phosphorus Radioisotopes ; Polycyclic Compounds ; Tetradecanoylphorbol Acetate (NI40JAQ945)
Language	English
Publishing date	2003-08-22
Publishing country	Netherlands
Document type	Comparative Study ; Journal Article
ZDB-ID	206607-5
ISSN	1873-135X ; 0027-5107 ; 1383-5718 ; 0165-1110 ; 0165-1161 ; 0165-7992 ; 0921-8777 ; 0165-1218 ; 1383-5726 ; 0167-8817 ; 0921-8734 ; 1383-5742
ISSN (online)	1873-135X
ISSN	0027-5107 ; 1383-5718 ; 0165-1110 ; 0165-1161 ; 0165-7992 ; 0921-8777 ; 0165-1218 ; 1383-5726 ; 0167-8817 ; 0921-8734 ; 1383-5742
DOI	10.1016/s1383-5718(03)00178-5
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