Effects of benzene metabolite treatment on granulocytic differentiation and DNA adduct formation in HL-60 cells

Hedli, Christine C.; Rao, N R; Reuhl, K.; Witmer, Charlotte; Snyder, Robert

doi:10.1007/s002040050252

Cited by 26 publications

(17 citation statements)

References 25 publications

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“…We recently evaluated the significance of DNA adduct formation in toxicity by studying the effects of benzene metabolites on DNA adduct formation and retinoic acid-induced granulocytic differentiation in this model (38). Table 3 shows that while treatment of HL-60 cells with 50 ,uM hydroquinone for 1 to 4 hr induced the formation of a single DNA adduct that increased with increasing time of exposure, no adducts were detected in cells treated with 50 to 500 pM 1,2,4-benzenetriol for up to 4 hr.…”

Section: Microsomal Metabolismmentioning

confidence: 99%

An Overview of Benzene Metabolism

Snyder¹,

Hedli²

1996

Environ Health Perspect

105

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Benzene toxicity involves both bone marrow depression and leukemogenesis caused by damage to multiple classes of hematopoietic cells and a variety of hematopoietic cell functions. Study of the relationship between the metabolism and toxicity of benzene indicates that several metabolites of benzene play significant roles in generating benzene toxicity. Benzene is metabolized, primarily in the liver, to a variety of hydroxylated and ring-opened products that are transported to the bone marrow where subsequent secondary metabolism occurs. Two potential mechanisms by which benzene metabolites may damage cellular macromolecules to induce toxicity include the covalent binding of reactive metabolites of benzene and the capacity of benzene metabolites to induce oxidative damage. Although the relative contributions of each of these mechanisms to toxicity remains unestablished, it is clear that different mechanisms contribute to the toxicities associated with different metabolites. As a corollary, it is unlikely that benzene toxicity can be described as the result of the interaction of a single metabolite with a single biological target. Continued investigation of the metabolism of benzene and its metabolites will allow us to determine the specific combination of metabolites as well as the biological target(s) involved in toxicity and will ultimately lead to our understanding of the relationship between the production of benzene metabolites and bone marrow toxicity.

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Section: Microsomal Metabolismmentioning

confidence: 99%

An Overview of Benzene Metabolism

Snyder¹,

Hedli²

1996

Environ Health Perspect

105

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“…The observed increase in white blood cells and platelets count could be attributed to acute response of the myeloid and megakaryotic stem cells to high dosage of the oil. Studies have shown that these stem cells have the selective advantage of proliferation and resistance to acute toxicity of crude oil and its metabolites 16,[32][33] .…”

Section: Resultsmentioning

confidence: 99%

“…The metabolites of benzene and polycyclic aromatic hydrocarbon have been shown to be very potent carcinogens [16][17][18] . The present study, investigates the effect of Bonny light crude oil on some hematological parameters in guinea pigs.…”

Section: Introductionmentioning

confidence: 99%

Effect of bonny light crude oil on some haematological parameters of guinea pigs

et al. 2006

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The effect of Bonny light crude oil on some haematological parameters (red cell count, white cell count, platelet count, packed cell volume and hemoglobin concentration) were studied in guinea pigs. The two experimental groups were gavaged with 4ml/kg and 6ml/kg respectively for seven days while the control group was gavaged with olive oil (6ml/kg) for seven days. The red cell count in the 4ml/Kg group was significantly lower (P<0.05) when compared with control and 6ml/Kg group. The platelet count showed statistically significant difference (P<0.05) when the two test groups were compared with the control and also when compared to each other (P<0.05). Haemoglobin concentrations were significantly increased (P<0.05) in high dose group compared with low dose group and control. There were no significant differences in haemoglobin concentrations of low dose group when compared with control. The results indicate that gavaging of guinea pigs with Bonny light crude oil cause changes in some hematological parameters due to the injurious effect of the toxic components of the crude oil.

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“…DNA damage, formation of DNA adducts, chromosomal aberrations such as aneuploidy, increased formation of micronuclei and sister chromatid exchanges) of benzene and its metabolites (namely HQ, 1,4-BQ, 1,2,4-BT and catechol) is the most reported key event observed in the identified in vitro studies Bodell et al, 1996;Chung et al, 2002;Hedli et al, 1996;Ishihama et al, 2008;Levay & Bodell, 1992;Levay et al, 1993;Lindsey et al, 2005;Lindsey et al, 2004;Mondrala & Eastmond, 2010;Oikawa et al, 2001;Pandey et al, 2009;Pasquini et al, 2003;Thys et al, 2015;Winn, 2003;Zhang et al, 1993;Zhang et al, 1994;Zhang et al, 1998). Then it is followed by oxidative stress as an early key event associated with benzene and its metabolites (Badham & Winn, 2010a;Goldman et al, 1999;Ishihama et al, 2008;Kolachana et al, 1993;Li & Trush, 1993;Nishikawa et al, 2012;Oikawa et al, 2001;Ruiz-Ramos et al, 2005;Wan & Winn, 2007;Wiemels & Smith, 1999;Zhang et al, 1993).…”

Section: Supporting Publications 2016: En-955 129mentioning

confidence: 99%

Systematic literature review on Parkinson's disease and Childhood Leukaemia and mode of actions for pesticides

Choi¹,

Polcher²,

Joas³

2016

EFSA Supporting Publications

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This report presents the outcomes of a systematic review (SR) identifying the mechanisms and chemicals involved in the pathogenesis of Parkinson's disease (PD) and childhood leukaemia (CL). This work serves as a basis for defining and mapping the causal linkages between a molecular initiating event (MIE) and a final adverse outcome (AO) that are relevant for the development of a prototype adverse outcome pathway (AOP) for assessing risk factors for PD and CL. Search for literature from 1990 to present was conducted using Web of Science, PubMed and TOXNET, and relevant references were selected using established inclusion/exclusion criteria and ranked using a set of quality control factors.For PD, 7,384 individual references were identified to be relevant for PD pathogenesis and chemicals associated with PD. Dopaminergic neurodegeneration in the substantia nigra leading to locomotor deficits was identified as the AO in PD. Other identified key events in PD pathogenesis include mitochondrial dysfunction, cellular accumulation of alpha-synuclein and oxidative stress. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, rotenone and paraquat are some chemicals identified to be associated with PD pathogenesis.For CL, 1,988 individual references were identified to be relevant for CL pathogenesis and chemicals associated with CL. Chromosomal translocation, genetic damage/mutation and hyperdiploidy are considered as driving forces of CL. Except for infant leukaemia, CL pathogenesis requires a 'two-hit' model with an initiating event occurring in utero followed by a secondary hit potentially occurring after birth. Potential MIEs leading to these driving mechanisms include aberrant DNA topoisomerase II activity and erroneous DNA repair. Epigenetics appears to also play an influential role in CL pathogenesis. Benzene, bioflavonoids and organophosphates are some chemicals identified to be implicated in CL pathogenesis.The challenges of developing AOPs for these two diseases and the data gaps identified from the outcomes of this SR are also elaborated in this report. The present document has been produced and adopted by the bodies identified above as authors. This task has been carried out exclusively by the authors in the context of a contract between the European Food Safety Authority and the authors, awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. KEY WORDSSystematic Review, Parkinson Disease, Childhood Leukaemia, Pathogenesis, Chemicals, Pesticides, Adverse Outcome Pathway SUMMARYThe aim of this project was to perform a systematic review (SR) to collect relevant publications related to the mechanisms involved in the pathogenesis of Parkinson's disease (PD)...

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Effects of benzene metabolite treatment on granulocytic differentiation and DNA adduct formation in HL-60 cells

Cited by 26 publications

References 25 publications

An Overview of Benzene Metabolism

An Overview of Benzene Metabolism

Effect of bonny light crude oil on some haematological parameters of guinea pigs

Systematic literature review on Parkinson's disease and Childhood Leukaemia and mode of actions for pesticides

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