77
Views
93
CrossRef citations to date
0
Altmetric
Research Article

A Perspective on Benzene Leukemogenesis

&
Pages 177-209 | Published online: 25 Sep 2008

Keep up to date with the latest research on this topic with citation updates for this article.

Read on this site (9)

David W. Pyatt, Sean M. Hays, Christine English & Colleen A. Cushing. (2012) United States voluntary children’s chemical evaluation program (VCCEP) risk assessment for children exposed to benzene. Toxicology Mechanisms and Methods 22:2, pages 81-104.
Read now
Robert Golden, David Pyatt & Peter G. Shields. (2006) Formaldehyde as a Potential Human Leukemogen: An Assessment of Biological Plausibility. Critical Reviews in Toxicology 36:2, pages 135-153.
Read now
Robert Snyder. (2004) Xenobiotic Metabolism and the Mechanism(s) of Benzene Toxicity. Drug Metabolism Reviews 36:3-4, pages 531-547.
Read now
Robert Snyder. (2000) RECENT DEVELOPMENTS IN THE UNDERSTANDING OF BENZENE TOXICITY AND LEUKEMOGENESIS. Drug and Chemical Toxicology 23:1, pages 13-25.
Read now
Jingsheng Tuo, Xingsheng Deng, Steffen Loft & Henrik E. Poulsen. (1999) Dexamethasone ameliorates oxidative DNA damage induced by benzene and LPS in mouse bone marrow. Free Radical Research 30:1, pages 29-36.
Read now
Anthony P. DeCaprio. (1999) The Toxicology of Hydroquinone — Relevance to Occupational and Environmental Exposure. Critical Reviews in Toxicology 29:3, pages 283-330.
Read now
P. Hotz & Robert R. Lauwerys. (1997) Hematopoietic and Lymphatic Malignancies in Vehicle Mechanics. Critical Reviews in Toxicology 27:5, pages 443-494.
Read now
Rodney R. Dietert & Alan Hedge. (1996) Toxicological Considerations in Evaluating Indoor Air Quality and Human Health: Impact of New Carpet Emissions. Critical Reviews in Toxicology 26:6, pages 633-707.
Read now
Hong Zhu, Yunbo Li & MichaelA. Trush. (1995) Differences in xenobiotic detoxifying activities between bone marrow stromal cells from mice and rats: Implications for benzene‐induced hematotoxicity. Journal of Toxicology and Environmental Health 46:2, pages 183-201.
Read now

Articles from other publishers (84)

Gui Zhang, Lunkai Li, Yuqin Yang, Li Song, Guangrong Kuang & Yingzi Fu. (2023) Electrochemiluminescence biosensing of spatially conjugated ester groups triggered by smart bridging between nano-silica and poly (ethylene maleate). Sensors and Actuators B: Chemical, pages 134346.
Crossref
Qianyu Sun, Boshen Wang, Shouxiang Xu, Xiaowei Cong, Yuepu Pu & Juan Zhang. (2022) Research development and trends of benzene-induced leukemia from 1990 to 2019-A bibliometric analysis. Environmental Science and Pollution Research 29:7, pages 9626-9639.
Crossref
R Dewi, Z Abdul Hamid, NF Rajab, S Shuib & SR Abdul Razak. (2019) Genetic, epigenetic, and lineage-directed mechanisms in benzene-induced malignancies and hematotoxicity targeting hematopoietic stem cells niche. Human & Experimental Toxicology 39:5, pages 577-595.
Crossref
Karin C. Nitiss, John L. Nitiss & Leslyn A. Hanakahi. (2019) DNA Damage by an essential enzyme: A delicate balance act on the tightrope. DNA Repair 82, pages 102639.
Crossref
Davood Farmanzadeh & Azadeh Valipour. (2018) Pure and M-doped (M=Zn, Cu, Ni, Co) cadmium oxide nanosheets, novel adsorbents for the adsorption of ethyl benzene and ortho, meta, para xylene: a theoretical study. Adsorption 25:1, pages 51-62.
Crossref
Davood Farmanzadeh & Azadeh Valipour. (2018) Adsorption of benzene and toluene molecules on surface of pure and doped cadmium oxide nanosheets: A computational investigation. Applied Surface Science 450, pages 509-515.
Crossref
Bahram Harati, Seyed Jamaleddin Shahtaheri, Ali Karimi, Kamal Azam, Ali Harati, Alireza Ahmadi & Maryam Afzali Rad. (2017) Hematologic Evaluation of Painting Hall Workers in an Automobile Manufacturing Company. Shiraz E-Medical Journal 18:12.
Crossref
Ercole L. Cavalieri & Eleanor G. Rogan. (2016) Depurinating estrogen‐DNA adducts, generators of cancer initiation: their minimization leads to cancer prevention. Clinical and Translational Medicine 5:1.
Crossref
Paik Wah Chow, Zariyantey Abdul Hamid, Kok Meng Chan, Salmaan Hussain Inayat-Hussain & Nor Fadilah Rajab. (2015) Lineage-related cytotoxicity and clonogenic profile of 1,4-benzoquinone-exposed hematopoietic stem and progenitor cells. Toxicology and Applied Pharmacology 284:1, pages 8-15.
Crossref
Ercole Cavalieri & Eleanor Rogan. (2014) The molecular etiology and prevention of estrogen-initiated cancers. Molecular Aspects of Medicine 36, pages 1-55.
Crossref
Atif Kamal & Riffat Naseem Malik. (2012) Hematological Evidence of Occupational Exposure to Chemicals and Other Factors among Auto-Repair Workers in Rawalpindi, Pakistan. Osong Public Health and Research Perspectives 3:4, pages 229-238.
Crossref
Robert Snyder. (2012) Leukemia and Benzene. International Journal of Environmental Research and Public Health 9:8, pages 2875-2893.
Crossref
. (2012) Occupational Exposure to Aromatic Hydrocarbons and Polycyclic Aromatic Hydrocarbons at a Coke Plant. The Annals of Occupational Hygiene.
Crossref
Gordon P. McCallum, Michelle Siu, Stephanie L. Ondovcik, J. Nicole Sweeting & Peter G. Wells. (2010) Methanol exposure does not lead to accumulation of oxidative DNA damage in bone marrow and spleen of mice, rabbits or primates. Molecular Carcinogenesis 50:3, pages 163-172.
Crossref
Martino Amodio, Gianluigi de Gennaro, Annalisa Marzocca, Livia Trizio & Maria Tutino. (2011) Monitoring of volatile organic compounds in the cities of the metropolitan area of Bari (Italy). Procedia Environmental Sciences 4, pages 126-133.
Crossref
Maurizio Caselli, Gianluigi de Gennaro, Annalisa Marzocca, Livia Trizio & Maria Tutino. (2010) Assessment of the impact of the vehicular traffic on BTEX concentration in ring roads in urban areas of Bari (Italy). Chemosphere 81:3, pages 306-311.
Crossref
Benjamin Smith, Peter Cadby, Michael DiNovi & R. Woodrow Setzer. (2010) Application of the Margin of Exposure (MoE) approach to substances in food that are genotoxic and carcinogenic. Food and Chemical Toxicology 48, pages S49-S56.
Crossref
Håkon L. Leira, Frode Fonnum & Tore Syversen. 2009. General, Applied and Systems Toxicology. General, Applied and Systems Toxicology.
Timothy C. Marrs & Simon Warren. 2009. General, Applied and Systems Toxicology. General, Applied and Systems Toxicology.
Alok Kumar Pandey, Deepak Gurbani, Mahima Bajpayee, Devendra Parmar, Subhash Ajmani & Alok Dhawan. (2009) In silico studies with human DNA topoisomerase-II alpha to unravel the mechanism of in vitro genotoxicity of benzene and its metabolites. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 661:1-2, pages 57-70.
Crossref
Paolo Bruno, Maurizio Caselli, Gianluigi de Gennaro, Lucia Scolletta, Livia Trizio & Maria Tutino. (2008) Assessment of the Impact Produced by the Traffic Source on VOC Level in the Urban Area of Canosa di Puglia (Italy). Water, Air, and Soil Pollution 193:1-4, pages 37-50.
Crossref
Patrick Beatty. 2007. Encyclopedia of Quantitative Risk Analysis and Assessment. Encyclopedia of Quantitative Risk Analysis and Assessment.
S Wilbur, D Wohlers, S Paikoff, LS Keith & O Faroon. (2008) ATSDR evaluation of health effects of benzene and relevance to public health. Toxicology and Industrial Health 24:5-6, pages 263-398.
Crossref
Ijaz S. Jamall & Calvin C. Willhite. (2008) Is benzene exposure from gasoline carcinogenic?. J. Environ. Monit. 10:2, pages 176-187.
Crossref
Faramarz Naeim & P. Nagesh Rao. 2008. Hematopathology. Hematopathology 207 255 .
A. Kathleen McClendon & Neil Osheroff. (2007) DNA topoisomerase II, genotoxicity, and cancer. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 623:1-2, pages 83-97.
Crossref
David Kokel & Ding Xue. (2006) A Class of Benzenoid Chemicals Suppresses Apoptosis in C. elegans. ChemBioChem 7:12, pages 2010-2015.
Crossref
E. CAVALIERI & E. ROGAN. (2006) Catechol Quinones of Estrogens in the Initiation of Breast, Prostate, and Other Human Cancers: Keynote Lecture. Annals of the New York Academy of Sciences 1089:1, pages 286-301.
Crossref
Joseph Landolph, Xue Weiling & David Warshawsky. 2005. Molecular Carcinogenesis and the Molecular Biology of Human Cancer. Molecular Carcinogenesis and the Molecular Biology of Human Cancer 25 44 .
Mamdouh S. Masoud, Alaa E. Ali, Medhat A. Shaker & Mohamed Abdul Ghani. (2005) Solvent and substituent effects on spectroscopical changes of some diazoaminobenzene derivatives. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 61:13-14, pages 3102-3107.
Crossref
R. Hunter Lindsey, Ryan P. Bender & Neil Osheroff. (2005) Stimulation of topoisomerase II-mediated DNA cleavage by benzene metabolites. Chemico-Biological Interactions 153-154, pages 197-205.
Crossref
David W. Pyatt, Sean M. Hays & Colleen A. Cushing. (2005) Do children have increased susceptibility for developing secondary acute myelogenous leukemia?. Chemico-Biological Interactions 153-154, pages 223-229.
Crossref
R. Hunter Lindsey, Ryan P. Bender & Neil Osheroff. (2005) Effects of Benzene Metabolites on DNA Cleavage Mediated by Human Topoisomerase IIα:  1,4-Hydroquinone Is a Topoisomerase II Poison. Chemical Research in Toxicology 18:4, pages 761-770.
Crossref
E.B. Murray & J.W. Edwards. (2005) Differential Induction of Micronuclei in Peripheral Blood Lymphocytes and Exfoliated Urothelial Cells of Workers Exposed to 4,4'-methylenebis-(2-chloroaniline) (MOCA) and Bitumen Fumes. Reviews on Environmental Health 20:3.
Crossref
V. Simon, M. Baer, L. Torres, S. Olivier, M. Meybeck & J.P. Della Massa. (2004) The impact of reduction in the benzene limit value in gasoline on airborne benzene, toluene and xylenes levels. Science of The Total Environment 334-335, pages 177-183.
Crossref
Daiva Bironaite, David Siegel, Julie L. Moran, Babette B. Weksler & David Ross. (2004) Stimulation of endothelial IL-8 (eIL-8) production and apoptosis by phenolic metabolites of benzene in HL-60 cells and human bone marrow endothelial cells. Chemico-Biological Interactions 149:2-3, pages 177-188.
Crossref
Miriam C. Poirier. (2004) Chemical-induced DNA damage and human cancer risk. Nature Reviews Cancer 4:8, pages 630-637.
Crossref
Daiva Bironaite, David Siegel, Julie L. Moran, Babette B. Weksler & David Ross. (2004) Stimulation of endothelial IL-8 (eIL-8) production and apoptosis by phenolic metabolites of benzene in HL-60 cells and human bone marrow endothelial cells. Chemico-Biological Interactions 149:1, pages 37-49.
Crossref
R. Hunter Lindsey,, Kenneth D. Bromberg, Carolyn A. Felix & Neil Osheroff. (2004) 1,4-Benzoquinone Is a Topoisomerase II Poison. Biochemistry 43:23, pages 7563-7574.
Crossref
Jacqueline Fung, Matthew J. Hoffmann, David D. Kim & Robert Snyder. (2004) Inhibition of topoisomerase II in 32D.3(G) cells by hydroquinone is associated with cell death. Journal of Applied Toxicology 24:3, pages 183-188.
Crossref
Veronica C Nwosu, Grace E Kissling, Carol S Trempus, Hayden Honeycutt & John E French. (2004) Exposure of Tg.AC transgenic mice to benzene suppresses hematopoietic progenitor cells and alters gene expression in critical signaling pathways. Toxicology and Applied Pharmacology 196:1, pages 37-46.
Crossref
John Whysner, M Vijayaraj Reddy, Peter M Ross, Melissa Mohan & Elizabeth A Lax. (2004) Genotoxicity of benzene and its metabolites. Mutation Research/Reviews in Mutation Research 566:2, pages 99-130.
Crossref
Mary Ellen Fleming-Jones & Robert E. Smith. (2003) Volatile Organic Compounds in Foods:  A Five Year Study. Journal of Agricultural and Food Chemistry 51:27, pages 8120-8127.
Crossref
Jiayu Chen, Weiwei Liu, Xiaohuai Wang, Huaiyu Chen, Jinming Wu, Yi Yang, Lubo Wu & Demao Yang. (2003) Ex Vivo Immunotherapy for Patients with Benzene-Induced Aplastic Anemia. Journal of Hematotherapy & Stem Cell Research 12:5, pages 505-514.
Crossref
Clifford P Weisel, Seongsoo Park, Heesoo Pyo, Krishnan Mohan & Gisela Witz. (2003) Use of stable isotopically labeled benzene to evaluate environmental exposures. Journal of Exposure Science & Environmental Epidemiology 13:5, pages 393-402.
Crossref
Byung-Il YoonGuang-Xun LiKunio KitadaYasushi KawasakiKatsuhide IgarashiYukio KodamaTomoaki InoueKazuko KobayashiJun KannoDae-Yong KimTohru InoueYoko Hirabayashi. (2003) Mechanisms of benzene-induced hematotoxicity and leukemogenicity: cDNA microarray analyses using mouse bone marrow tissue.. Environmental Health Perspectives 111:11, pages 1411-1420.
Crossref
Yuko Ueno, Tsutomu Horiuchi, Masato Tomita, Osamu Niwa, Hao-shen Zhou, Takeo Yamada & Itaru Honma. (2002) Separate Detection of BTX Mixture Gas by a Microfluidic Device Using a Function of Nanosized Pores of Mesoporous Silica Adsorbent. Analytical Chemistry 74:20, pages 5257-5262.
Crossref
Assieh A. Melikian, Qingshan Qu, Roy Shore, Guilan Li, Heyi Li, Ximei Jin, Beverly Cohen, Lungchi Chen, Yuying Li, Songnian Yin, Reidong Mu, Xiaoling Zhang & Yuanxiang Wang. (2002) Personal exposure to different levels of benzene and its relationships to the urinary metabolites S-phenylmercapturic acid and trans,trans-muconic acid. Journal of Chromatography B 778:1-2, pages 211-221.
Crossref
J.B Laurens, X.Y Mbianda, J.H Spies, J.B Ubbink & W.J.H Vermaak. (2002) Validated method for quantitation of biomarkers for benzene and its alkylated analogues in urine. Journal of Chromatography B 774:2, pages 173-185.
Crossref
Ercole L. Cavalieri, Kai-Ming Li, Narayanan Balu, Muhammad Saeed, Prabu Devanesan, Sheila Higginbotham, John Zhao, Michael L. Gross & Eleanor G. Rogan. (2002) Catechol ortho-quinones: the electrophilic compounds that form depurinating DNA adducts and could initiate cancer and other diseases. Carcinogenesis 23:6, pages 1071-1077.
Crossref
Jürgen Fuchs & Lester PackerJürgen Fuchs. 2001. Environmental Stressors in Health and Disease. Environmental Stressors in Health and Disease.
Matthew J. Hoffmann, Patrick J. Sinko, Yong-Hee Lee, Robert J. Meeker & Robert Snyder. (2001) Pharmacokinetic Studies in Tg.AC and FVB Mice Administered [14C]Benzene either by Oral Gavage or Intradermal Injection. Toxicology and Applied Pharmacology 174:2, pages 139-145.
Crossref
Robert G. Tardiff. 2001. Patty's Industrial Hygiene. Patty's Industrial Hygiene.
R Henschler, K.E Appel, C.M Heyworth & H Glatt. (2001) Proliferation and differentiation of murine haemopoietic progenitor cells in stroma-free culture in the presence of metabolites of chlorinated pesticides. Toxicology in Vitro 15:1, pages 31-37.
Crossref
TA McDonald, NT Holland, C Skibola, P Duramad & MT Smith. (2001) Hypothesis: Phenol and hydroquinone derived mainly from diet and gastrointestinal flora activity are causal factors in leukemia. Leukemia 15:1, pages 10-20.
Crossref
Matthew J. Hoffmann, Patrick J. Sinko, Robert J. Meeker & Robert Snyder. 2001. Biological Reactive Intermediates VI. Biological Reactive Intermediates VI 455 458 .
George F. Kalf, Betsy A. Hazel, Matthew J. Hoffmann, David D. Kim & Robert Snyder. 2001. Biological Reactive Intermediates VI. Biological Reactive Intermediates VI 429 439 .
Matthew J. Hoffmann, David D. Kim, Mohammed G. K. Akbar, George F. Kalf & Robert Snyder. 2001. Biological Reactive Intermediates VI. Biological Reactive Intermediates VI 315 318 .
Roberto Fabiani, Angelo De Bartolomeo, Patrizia Rosignoli, Michela Scamosci, Luca Lepore & Guido Morozzi. (2001) Influence of culture conditions on the DNA-damaging effect of benzene and its metabolites in human peripheral blood mononuclear cells. Environmental and Molecular Mutagenesis 37:1, pages 1-6.
Crossref
Chitra Mani, Stewart Freeman, David O. Nelson, John S. Vogel & Kenneth W. Turteltaub. (1999) Species and Strain Comparisons in the Macromolecular Binding of Extremely Low Doses of [14C]Benzene in Rodents, Using Accelerator Mass Spectrometry. Toxicology and Applied Pharmacology 159:2, pages 83-90.
Crossref
Jingsheng Tuo, Steffen Loft & Henrik E Poulsen. (1999) Enhanced benzene-induced DNA damage in PMA-stimulated cells in vitro and in LPS-treated animals. Free Radical Biology and Medicine 26:7-8, pages 801-808.
Crossref
Lesley Rushton & Kathleen Cameron. 1999. Air Pollution and Health. Air Pollution and Health 813 838 .
N. Rothman, W. E. Bechtold, S. N. Yin, M. Dosemeci, G. L. Li, Y. Z. Wang, W. C. Griffith, M. T. Smith & R. B. Hayes. (1998) Urinary excretion of phenol, catechol, hydroquinone, and muconic acid by workers occupationally exposed to benzene. Occupational and Environmental Medicine 55:10, pages 705-711.
Crossref
Andrew B. LindstromKaren Yeowell-O'ConnellSuramya WaidyanathaThomas A. McDonaldBernard T. GoldingStephen M. Rappaport. (1998) Formation of Hemoglobin and Albumin Adducts of Benzene Oxide in Mouse, Rat, and Human Blood. Chemical Research in Toxicology 11:4, pages 302-310.
Crossref
L CaprinoG I Togna. (1998) Potential health effects of gasoline and its constituents: A review of current literature (1990-1997) on toxicological data.. Environmental Health Perspectives 106:3, pages 115-125.
Crossref
URVASHI RANGAN & ROBERT SNYDER. (1997) Scientific Update on Benzenea. Annals of the New York Academy of Sciences 837:1, pages 105-112.
Crossref
Urvashi RanganChristine HedliMichael GalloPaul LioyRobert Snyder. (2016) Exposure and Risk Assessment with Respect to Contaminated Soil: Significance of Biomarkers and Bioavailability. International Journal of Toxicology 16:4-5, pages 419-432.
Crossref
Xin-sheng Deng, Jinsheng Tuo, Henrik E Poulsen & Steffen Loft. (1997) 2-Nitropropane-induced DNA damage in rat bone marrow. Mutation Research/Genetic Toxicology and Environmental Mutagenesis 391:3, pages 165-169.
Crossref
M A Medinsky, E M Kenyon, M J Seaton & P M Schlosser. (1996) Mechanistic considerations in benzene physiological model development.. Environmental Health Perspectives 104:suppl 6, pages 1399-1404.
Crossref
G K Raabe & O Wong. (1996) Leukemia mortality by cell type in petroleum workers with potential exposure to benzene.. Environmental Health Perspectives 104:suppl 6, pages 1381-1392.
Crossref
F A Angelosanto, G R Blackburn, C A Schreiner & C R Mackerer. (1996) Benzene induces a dose-responsive increase in the frequency of micronucleated cells in rat Zymbal glands.. Environmental Health Perspectives 104:suppl 6, pages 1331-1336.
Crossref
A M HuttG F Kalf. (1996) Inhibition of human DNA topoisomerase II by hydroquinone and p-benzoquinone, reactive metabolites of benzene.. Environmental Health Perspectives 104:suppl 6, pages 1265-1269.
Crossref
B A HazelA O'ConnorR NiculescuG F Kalf. (1996) Induction of granulocytic differentiation in a mouse model by benzene and hydroquinone.. Environmental Health Perspectives 104:suppl 6, pages 1257-1264.
Crossref
G Witz, Z Zhang & B D Goldstein. (1996) Reactive ring-opened aldehyde metabolites in benzene hematotoxicity.. Environmental Health Perspectives 104:suppl 6, pages 1195-1199.
Crossref
W J BodellD N PathakG LévayQ YeK Pongracz. (1996) Investigation of the DNA adducts formed in B6C3F1 mice treated with benzene: implications for molecular dosimetry.. Environmental Health Perspectives 104:suppl 6, pages 1189-1193.
Crossref
R Snyder & C C Hedli. (1996) An overview of benzene metabolism.. Environmental Health Perspectives 104:suppl 6, pages 1165-1171.
Crossref
P J BoogaardN J van Sittert. (1996) Suitability of S-phenyl mercapturic acid and trans-trans-muconic acid as biomarkers for exposure to low concentrations of benzene.. Environmental Health Perspectives 104:suppl 6, pages 1151-1157.
Crossref
A. Robert Schnatter, Mark J. Nicolich & Michael G. Bird. (2006) Determination of Leukemogenic Benzene Exposure Concentrations: Refined Analyses of the Pliofilm Cohort. Risk Analysis 16:6, pages 833-840.
Crossref
Betsy A. Hazel, Christine Baum & George F. Kalf. (2009) Hydroquinone, a Bioreactive Metabolite of Benzene, Inhibits Apoptosis in Myeloblasts. STEM CELLS 14:6, pages 730-742.
Crossref
Jean A. Grassman. (1996) Obtaining information about susceptibility from the epidemiological literature. Toxicology 111:1-3, pages 253-270.
Crossref
Martyn T. Smith. 1996. Biological Reactive Intermediates V. Biological Reactive Intermediates V 259 266 .
Avishay-Abraham Stark & William H. Rastetter. (1996) Structure-activity relationships in the mutagenicity and cytotoxicity of putative metabolites and related analogs of benzene derived from the valence tautomers benzene oxide and oxepin. Environmental and Molecular Mutagenesis 28:3, pages 284-293.
Crossref
Betsy A. Hazel, Annette O'Connor, Rodica Niculescu & George F. Kalf. (2008) Benzene and its metabolite, hydroquinone, induce granulocytic differentiation in myeloblasts by interacting with cellular signaling pathways activated by granulocyte colony‐stimulating factor. STEM CELLS 13:3, pages 295-310.
Crossref
D. Anderson, T.‐W. Yu & P. Schmezer. (2006) An investigation of the DNA‐damaging ability of benzene and its metabolites in human lymphocytes, using the comet assay. Environmental and Molecular Mutagenesis 26:4, pages 305-314.
Crossref

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.