Advances in understanding benzene health effects and susceptibility.

Benzene is a ubiquitous chemical in our environment that causes acute leukemia and probably other hematological cancers. Evidence for an association with childhood leukemia is growing. Exposure to benzene can lead to multiple alterations that contribute to the leukemogenic process, indicating a multimodal mechanism of action. Research is needed to elucidate the different roles of multiple metabolites in benzene toxicity and the pathways that lead to their formation. Studies to date have identified a number of polymorphisms in candidate genes that confer susceptibility to benzene hematotoxicity. However, a genome-wide study is needed to truly assess the role of genetic variation in susceptibility. Benzene affects the blood-forming system at low levels of occupational exposure, and there is no evidence of a threshold. There is probably no safe level of exposure to benzene, and all exposures constitute some risk in a linear, if not supralinear, and additive fashion.

[1]  D. Thomas,et al.  Methods for investigating gene-environment interactions in candidate pathway and genome-wide association studies. , 2010, Annual review of public health.

[2]  Muin J. Khoury,et al.  Family history in public health practice: a genomic tool for disease prevention and health promotion. , 2010, Annual review of public health.

[3]  Debra Rog,et al.  Evaluability assessment to improve public health policies, programs, and practices. , 2010, Annual review of public health.

[4]  L. Koehly,et al.  The behavioral response to personalized genetic information: will genetic risk profiles motivate individuals and families to choose more healthful behaviors? , 2010, Annual review of public health.

[5]  K. Glanz,et al.  The role of behavioral science theory in development and implementation of public health interventions. , 2010, Annual review of public health.

[6]  Neil E Caporaso,et al.  B-cell clones as early markers for chronic lymphocytic leukemia. , 2009, The New England journal of medicine.

[7]  Ken Chen,et al.  Recurring mutations found by sequencing an acute myeloid leukemia genome. , 2009, The New England journal of medicine.

[8]  J. Kitzman,et al.  Acquired copy number alterations in adult acute myeloid leukemia genomes , 2009, Proceedings of the National Academy of Sciences.

[9]  C. Bloomfield,et al.  The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. , 2009, Blood.

[10]  J. Cerhan,et al.  Pesticide exposure and risk of monoclonal gammopathy of undetermined significance in the Agricultural Health Study. , 2009, Blood.

[11]  N. Rothman,et al.  Association of Genetic Polymorphisms, mRNA Expression of p53 and p21 with Chronic Benzene Poisoning in a Chinese Occupational Population , 2009, Cancer Epidemiology Biomarkers & Prevention.

[12]  L. Winn,et al.  In utero and acute exposure to benzene: investigation of DNA double-strand breaks and DNA recombination in mice. , 2009, Mutation research.

[13]  R. Howard,et al.  A monoclonal gammopathy precedes multiple myeloma in most patients. , 2009, Blood.

[14]  Steven G. Gilbert,et al.  Doubt Is Their Product: How Industry’s Assault on Science Threatens Your Health , 2009, Environmental Health Perspectives.

[15]  Y. Q. Li,et al.  Decreased T‐cell receptor excision DNA circles in peripheral blood mononuclear cells among benzene‐exposed workers , 2009, International journal of immunogenetics.

[16]  U. Germing,et al.  Paradigmenwechsel in der Beurteilung myeloischer und lymphatischer Neoplasien bei beruflicher Benzolexposition (BK-Ziffer 1303) , 2009, Medizinische Klinik.

[17]  Nathaniel Rothman,et al.  Evidence That Humans Metabolize Benzene via Two Pathways , 2009, Environmental health perspectives.

[18]  L. Opanashuk,et al.  The aryl hydrocarbon receptor has a normal function in the regulation of hematopoietic and other stem/progenitor cell populations. , 2009, Biochemical pharmacology.

[19]  Y. Hirabayashi,et al.  Aryl hydrocarbon receptor biology and xenobiotic responses in hematopoietic progenitor cells. , 2009, Biochemical pharmacology.

[20]  D Hémon,et al.  Acute childhood leukaemia and residence next to petrol stations and automotive repair garages: the ESCALE study (SFCE) , 2009, Occupational and Environmental Medicine.

[21]  Luoping Zhang,et al.  Werner syndrome protein, WRN, protects cells from DNA damage induced by the benzene metabolite hydroquinone. , 2009, Toxicological sciences : an official journal of the Society of Toxicology.

[22]  J. Cho Suppressive Effect of Hydroquinone, a Benzene Metabolite, on In Vitro Inflammatory Responses Mediated by Macrophages, Monocytes, and Lymphocytes , 2009, Mediators of inflammation.

[23]  N. Osheroff,et al.  The DNA cleavage reaction of topoisomerase II: wolf in sheep's clothing , 2008, Nucleic acids research.

[24]  E. Taioli,et al.  NQO1, MPO, CYP2E1, GSTT1 and GSTM1 polymorphisms and biological effects of benzene exposure--a literature review. , 2008, Toxicology letters.

[25]  Amy E. Hawkins,et al.  DNA sequencing of a cytogenetically normal acute myeloid leukemia genome , 2008, Nature.

[26]  Steve Selvin,et al.  Research | Children’s Health Household Exposure to Paint and Petroleum Solvents, Chromosomal Translocations, and the Risk of Childhood Leukemia , 2008 .

[27]  E. Symanski,et al.  Childhood Lymphohematopoietic Cancer Incidence and Hazardous Air Pollutants in Southeast Texas, 1995–2004 , 2008, Environmental health perspectives.

[28]  U. Germing,et al.  [Practice of recognizing benzene-caused occupational diseases in 2006]. , 2008, Medizinische Klinik.

[29]  Y. Fujii‐Kuriyama,et al.  Benzene-induced hematopoietic toxicity transmitted by AhR in wild-type mouse and nullified by repopulation with AhR-deficient bone marrow cells: time after benzene treatment and recovery. , 2008, Chemosphere.

[30]  C. Bloomfield,et al.  Clinical significance of the most common chromosome translocations in adult acute myeloid leukemia. , 2008, Journal of the National Cancer Institute. Monographs.

[31]  T. Rabbitts,et al.  Modeling chromosomal translocations using conditional alleles to recapitulate initiating events in human leukemias. , 2008, Journal of the National Cancer Institute. Monographs.

[32]  Ø. Bruserud,et al.  Effects Of Benzene on Human Hematopoiesis , 2008 .

[33]  M. Varella‐Garcia,et al.  Multi-genetic events collaboratively contribute to Pten-null leukaemia stem-cell formation , 2008, Nature.

[34]  Guido Marcucci,et al.  Epigenetic modification of CCAAT/enhancer binding protein alpha expression in acute myeloid leukemia. , 2008, Cancer research.

[35]  A. Smith,et al.  Meta-analysis of benzene exposure and non-Hodgkin lymphoma: biases could mask an important association , 2008, Occupational and Environmental Medicine.

[36]  D. Christiansen,et al.  Genetics of therapy-related myelodysplasia and acute myeloid leukemia , 2008, Leukemia.

[37]  R. Irons,et al.  The TNF-alpha 238A polymorphism is associated with susceptibility to persistent bone marrow dysplasia following chronic exposure to benzene. , 2007, Leukemia research.

[38]  A. Hubbard,et al.  Aberrations in chromosomes associated with lymphoma and therapy‐related leukemia in benzene‐exposed workers , 2007, Environmental and molecular mutagenesis.

[39]  O. Faroon,et al.  ATSDR evaluation of health effects of benzene and relevance to public health , 2007, Toxicology and industrial health.

[40]  D. Eastmond,et al.  Differential cell cycle-specificity for chromosomal damage induced by merbarone and etoposide in V79 cells. , 2007, Mutation research.

[41]  G. Morgan,et al.  Non-Hodgkin Lymphoma Secondary to Cancer Chemotherapy , 2007, Cancer Epidemiology Biomarkers & Prevention.

[42]  Martyn T. Smith,et al.  Benzene Exposure and Risk of Non-Hodgkin Lymphoma , 2007, Cancer Epidemiology Biomarkers & Prevention.

[43]  Brunangelo Falini,et al.  Acute myeloid leukemia carrying cytoplasmic/mutated nucleophosmin (NPMc+ AML): biologic and clinical features. , 2007, Blood.

[44]  L. Hou,et al.  Changes in DNA methylation patterns in subjects exposed to low-dose benzene. , 2007, Cancer research.

[45]  Brent A. Johnson,et al.  Modeling Human Metabolism of Benzene Following Occupational and Environmental Exposures , 2006, Cancer Epidemiology Biomarkers & Prevention.

[46]  D. Christiansen,et al.  Alternative genetic pathways and cooperating genetic abnormalities in the pathogenesis of therapy-related myelodysplasia and acute myeloid leukemia , 2006, Leukemia.

[47]  S. Lamm,et al.  Benzene Exposure and Hematotoxicity , 2006, Science.

[48]  Alessandro Fatica,et al.  A Minicircuitry Comprised of MicroRNA-223 and Transcription Factors NFI-A and C/EBPα Regulates Human Granulopoiesis , 2005, Cell.

[49]  Kathryn Robinson,et al.  Benzene Exposures Associated with Tasks Performed on Marine Vessels (Circa 1975 to 2000) , 2005, Journal of occupational and environmental hygiene.

[50]  R. Hayes,et al.  Polymorphisms in cytokine and cellular adhesion molecule genes and susceptibility to hematotoxicity among workers exposed to benzene. , 2005, Cancer research.

[51]  W. P. Watson,et al.  Evidence for the formation of Michael adducts from reactions of (E,E)-muconaldehyde with glutathione and other thiols. , 2005, Bioorganic chemistry.

[52]  S. Rappaport,et al.  Investigation of cysteinyl protein adducts of benzene diolepoxide. , 2005, Chemico-biological interactions.

[53]  N. Rothman,et al.  Protein adducts as biomarkers of human benzene metabolism. , 2005, Chemico-biological interactions.

[54]  G. Morgan,et al.  Benzene and the hemopoietic stem cell. , 2005, Chemico-biological interactions.

[55]  R. Larson,et al.  Therapy-related myeloid leukaemia: a model for leukemogenesis in humans. , 2005, Chemico-biological interactions.

[56]  D. Eastmond,et al.  Topoisomerase II inhibition by myeloperoxidase-activated hydroquinone: a potential mechanism underlying the genotoxic and carcinogenic effects of benzene. , 2005, Chemico-biological interactions.

[57]  A. Jaiswal,et al.  Quinone oxidoreductases in protection against myelogenous hyperplasia and benzene toxicity. , 2005, Chemico-biological interactions.

[58]  M. Diaz,et al.  Surviving apoptosis: a possible mechanism of benzene-induced leukemia. , 2005, Chemico-biological interactions.

[59]  D. Jolley,et al.  Health Watch exposure estimates: do they underestimate benzene exposure? , 2005, Chemico-biological interactions.

[60]  E. Wright,et al.  Genotype-dependent induction of transmissible chromosomal instability by gamma-radiation and the benzene metabolite hydroquinone. , 2005, Cancer research.

[61]  M. Segal,et al.  DNA topoisomerase II in therapy-related acute promyelocytic leukemia. , 2005, The New England journal of medicine.

[62]  N. Osheroff,et al.  Effects of benzene metabolites on DNA cleavage mediated by human topoisomerase II alpha: 1,4-hydroquinone is a topoisomerase II poison. , 2005, Chemical research in toxicology.

[63]  R. Doll,et al.  Cancer risks in a historical UK cohort of benzene exposed workers , 2005, Occupational and Environmental Medicine.

[64]  G. Witz,et al.  Metabolites of benzene are potent inhibitors of gap-junction intercellular communication , 2005, Archives of Toxicology.

[65]  Nathaniel Rothman,et al.  Hematotoxicity in Workers Exposed to Low Levels of Benzene , 2004, Science.

[66]  R. Snyder Xenobiotic Metabolism and the Mechanism(s) of Benzene Toxicity , 2004, Drug metabolism reviews.

[67]  Lin Fritschi,et al.  Leukemia Risk Associated With Low-Level Benzene Exposure , 2003, Epidemiology.

[68]  M. Greaves,et al.  Origins of chromosome translocations in childhood leukaemia , 2003, Nature Reviews Cancer.

[69]  K. Matthay,et al.  Prenatal origin of childhood acute myeloid leukemias harboring chromosomal rearrangements t(15;17) and inv(16). , 2003, Blood.

[70]  Stephen Olin,et al.  The use of non-tumor data in cancer risk assessment: reflections on butadiene, vinyl chloride, and benzene. , 2003, Regulatory toxicology and pharmacology : RTP.

[71]  R W Hornung,et al.  Benzene exposure and hematopoietic mortality: A long-term epidemiologic risk assessment. , 2002, American journal of industrial medicine.

[72]  Y. Fujii‐Kuriyama,et al.  Aryl hydrocarbon receptor mediates benzene-induced hematotoxicity. , 2002, Toxicological sciences : an official journal of the Society of Toxicology.

[73]  R. Shore,et al.  Hematological changes among Chinese workers with a broad range of benzene exposures. , 2002, American journal of industrial medicine.

[74]  Ana-Teresa Maia,et al.  In utero origin of t(8;21) AML1-ETO translocations in childhood acute myeloid leukemia. , 2002, Blood.

[75]  R. Shore,et al.  Albumin adducts of benzene oxide and 1,4-benzoquinone as measures of human benzene metabolism. , 2002, Cancer research.

[76]  D. Eastmond,et al.  The Nature of Chromosomal Aberrations Detected in Humans Exposed to Benzene , 2002, Critical reviews in toxicology.

[77]  D. Pyatt,et al.  Benzene metabolites antagonize etoposide-stabilized cleavable complexes of DNA topoisomerase IIalpha. , 2001, Blood.

[78]  R. Hayes,et al.  Benzene and lymphohematopoietic malignancies in humans. , 2001, American journal of industrial medicine.

[79]  D C Glass,et al.  Validation of exposure estimation for benzene in the Australian petroleum industry , 2001, Toxicology and industrial health.

[80]  Martyn T. Smith,et al.  Benzene and lymphohematopoietic malignancies in China. , 2000, Journal of toxicology and environmental health. Part A.

[81]  D. Ross,et al.  THE ROLE OF METABOLISM AND SPECIFIC METABOLITES IN BENZENE-INDUCED TOXICITY: EVIDENCE AND ISSUES , 2000, Journal of toxicology and environmental health. Part A.

[82]  A. Hubbard,et al.  Hydroquinone, a benzene metabolite, increases the level of aneusomy of chromosomes 7 and 8 in human CD34-positive blood progenitor cells. , 2000, Carcinogenesis.

[83]  R. Irons,et al.  The benzene metabolite, hydroquinone, selectively induces 5q31- and -7 in human CD34+CD19- bone marrow cells. , 2000, Experimental hematology.

[84]  M. Greaves,et al.  Prenatal origin of acute lymphoblastic leukaemia in children , 1999, The Lancet.

[85]  P Stewart,et al.  Parental occupational exposure to hydrocarbons and risk of acute lymphocytic leukemia in offspring. , 1999, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[86]  M. Ingelman-Sundberg,et al.  Metabolism of benzene in human liver microsomes: individual variations in relation to CYP2E1 expression , 1999, Archives of Toxicology.

[87]  R. Hayes,et al.  Increased translocations and aneusomy in chromosomes 8 and 21 among workers exposed to benzene. , 1998, Cancer research.

[88]  M Dosemeci,et al.  Benzene and the dose-related incidence of hematologic neoplasms in China. Chinese Academy of Preventive Medicine--National Cancer Institute Benzene Study Group. , 1997, Journal of the National Cancer Institute.

[89]  Xi,et al.  Benzene poisoning, a risk factor for hematological malignancy, is associated with the NQO1 609C-->T mutation and rapid fractional excretion of chlorzoxazone. , 1997, Cancer research.

[90]  M B Paxton,et al.  Leukemia risk associated with benzene exposure in the Pliofilm cohort. , 1996, Environmental health perspectives.

[91]  R. Irons,et al.  The process of leukemogenesis. , 1996, Environmental health perspectives.

[92]  G. Kalf,et al.  Inhibition of human DNA topoisomerase II by hydroquinone and p-benzoquinone, reactive metabolites of benzene. , 1996, Environmental health perspectives.

[93]  Martyn T. Smith The mechanism of benzene-induced leukemia: a hypothesis and speculations on the causes of leukemia. , 1996, Environmental health perspectives.

[94]  M Dosemeci,et al.  An expanded cohort study of cancer among benzene-exposed workers in China. Benzene Study Group. , 1996, Environmental health perspectives.

[95]  J. Corton,et al.  Reduction of benzene metabolism and toxicity in mice that lack CYP2E1 expression. , 1996, Toxicology and applied pharmacology.

[96]  B. Zhang [Investigation of health status in workers exposed to low-level benzene]. , 1996, Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine].

[97]  W. Halperin,et al.  Risk of low red or white blood cell count related to estimated benzene exposure in a rubberworker cohort (1940-1975) , 1996, American journal of industrial medicine.

[98]  D. Eastmond,et al.  Topoisomerase inhibition by phenolic metabolites: a potential mechanism for benzene's clastogenic effects. , 1995, Carcinogenesis.

[99]  S. Rappaport,et al.  Production of benzoquinone adducts with hemoglobin and bone-marrow proteins following administration of [13C6]benzene to rats. , 1993, Carcinogenesis.

[100]  W. Bechtold,et al.  Biological markers of exposure to benzene: S-phenylcysteine in albumin. , 1992, Carcinogenesis.

[101]  D. Paustenbach,et al.  Reevaluation of benzene exposure for the Pliofilm (rubberworker) cohort (1936-1976). , 1992, Journal of toxicology and environmental health.

[102]  D. Colagiovanni,et al.  Synergistic action of the benzene metabolite hydroquinone on myelopoietic stimulating activity of granulocyte/macrophage colony-stimulating factor in vitro. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[103]  F E Alexander,et al.  Parental occupations of children with leukaemia in west Cumbria, north Humberside, and Gateshead. , 1991, BMJ.

[104]  M. Aksoy,et al.  Hematotoxicity and carcinogenicity of benzene. , 1989, Environmental health perspectives.

[105]  R. Hornung,et al.  Benzene and leukemia: an epidemiologic risk assessment. , 1989, Environmental health perspectives.

[106]  C. Du,et al.  Occupational exposure to benzene in China. , 1987, British journal of industrial medicine.

[107]  Y. J. Chen,et al.  Leukaemia in benzene workers: a retrospective cohort study. , 1987, British journal of industrial medicine.

[108]  H. Valkenburg,et al.  Childhood leukemia and parental occupation. A register-based case-control study. , 1985, American journal of epidemiology.

[109]  J. Wagoner,et al.  LEUKÆMIA IN BENZENE WORKERS , 1977, The Lancet.

[110]  M. Aksoy,et al.  Details of blood changes in 32 patients with pancytopenia associated with long-term exposure to benzene , 1972, British journal of industrial medicine.

[111]  A. Cappellini,et al.  Chromosome changes and their evolution in subjects with past exposure to benzene. , 1971, Archives of environmental health.

[112]  M. Aksoy,et al.  Haematological effects of chronic benzene poisoning in 217 workers , 1971, British journal of industrial medicine.

[113]  E. Cronkite,et al.  Evidence for radiation and chemicals as leukemogenic agents. , 1961, Archives of environmental health.

[114]  H. G. Weiskotten,et al.  The Action of Benzol : VI. Benzol Vapor Leucopenia (Rabbit). , 1920, The Journal of medical research.

[115]  L. Winn,et al.  In utero exposure to benzene disrupts fetal hematopoietic progenitor cell growth via reactive oxygen species. , 2010, Toxicological sciences : an official journal of the Society of Toxicology.

[116]  R. Hayes,et al.  Large-scale evaluation of candidate genes identifies associations between DNA repair and genomic maintenance and development of benzene hematotoxicity. , 2009, Carcinogenesis.

[117]  G. Carlson,et al.  Benzene metabolism in human lung cell lines BEAS‐2B and A549 and cells overexpressing CYP2F1 , 2004, Journal of biochemical and molecular toxicology.

[118]  S. Fröhling,et al.  Disruption of C/EBPalpha function in acute myeloid leukemia. , 2004, The New England journal of medicine.

[119]  A. Schnatter Benzene exposure and leukemia. , 2004, Epidemiology.

[120]  G. Carlson,et al.  Cytochromes P450 involved with benzene metabolism in hepatic and pulmonary microsomes , 2000, Journal of biochemical and molecular toxicology.

[121]  N. Rothman,et al.  Benzene increases aneuploidy in the lymphocytes of exposed workers: A comparison of data obtained by fluorescence in situ hybridization in interphase and metaphase cells , 1999, Environmental and molecular mutagenesis.

[122]  J. Fraumeni,et al.  Hematopoietic malignancies and related disorders among benzene-exposed workers in China. , 1994, Leukemia & lymphoma.

[123]  B. Goldstein Benzene toxicity. , 1988, Occupational medicine.

[124]  A. B. Smith,et al.  Leukemia in benzene workers. , 1981, American journal of industrial medicine.

[125]  M. Aksoy,et al.  AIDS and renal failure. , 1987, The New England journal of medicine.

[126]  P. Infante,et al.  Leukaemia in benzene workers. , 1977, Lancet.

[127]  A. Hamilton Benzene (Benzol) Poisoning. , 1931 .

[128]  Schwartz,et al.  The Action of Benzol , 1917 .

[129]  L. Selling Benzol as a leucotoxin : studies on the degeneration and regeneration of the blood and haematopoietic organs , 1913 .