Dysregulation of apoptosis by benzene metabolites and their relationships with carcinogenesis

IBUKI, Y

doi:10.1016/s0925-4439(04)00059-6

Cited by 3 publications

(3 citation statements)

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“…The recovery of colony formation by NAC treatment indicates that hydroquinone-induced genotoxic stress, followed by apoptosis, is involved in suppression of colony formation by hematopoietic stem or precursor cells, a process subverted by Fhit deficiency. The data show that Wt stem cell colony-forming ability was suppressed by hydroquinone, likely due to an increase in ROS by hydroquinone treatment (35,36), which causes DNA damage and apoptosis, whereas in the absence of Fhit ROS-induced DNA damage and apoptosis was reduced, leading to colony growth and mouse survival. This experiment accords with the recent demonstration that Fhit interacts with the ferredoxin reductase (Fdxr) protein (37), a 54-kDa mitochondrial flavoprotein responsible for transferring electrons from NADPH to cytochrome P450 via ferredoxin.…”

Section: Resultsmentioning

confidence: 90%

Fhit-Deficient Hematopoietic Stem Cells Survive Hydroquinone Exposure Carrying Precancerous Changes

Ishii¹,

Mimori²,

Ishikawa³

et al. 2008

Cancer Research

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The fragile FHIT gene is among the first targets of DNA damage in preneoplastic lesions, and recent studies have shown that Fhit protein is involved in surveillance of genome integrity and checkpoint response after genotoxin exposure. We now find that Fhit-deficient hematopoietic cells, exposed to the genotoxin hydroquinone, are resistant to the suppression of stem cell in vitro colony formation observed with wild-type (Wt) hematopoietic cells. In vivo-transplanted, hydroquinone-exposed, Fhit-deficient bone marrow cells also escaped the bone marrow suppression exhibited by Wt-transplanted bone marrow. Comparative immunohistochemical analyses of bone marrow transplants showed relative absence of Bax in Fhit-deficient bone marrow, suggesting insensitivity to apoptosis; assessment of DNA damage showed that occurrence of the oxidized base 8-hydroxyguanosine, a marker of DNA damage, was also reduced in Fhit-deficient bone marrow, as was production of intracellular reactive oxygen species. Treatment with the antioxidant N -acetyl-L-cysteine relieved hydroquinoneinduced suppression of colony formation by Wt hematopoietic cells, suggesting that the decreased oxidative damage to Fhitdeficient cells, relative to Wt hematopoietic cells, accounts for the survival advantage of Fhit-deficient bone marrow. Homology-dependent recombination repair predominated in Fhit-deficient cells, although not error-free repair, as indicated by a higher incidence of 6-thioguanine-resistant colonies. Tissues of hydroquinone-exposed Fhit-deficient bone marrow-transplanted mice exhibited preneoplastic alterations, including accumulation of histone H2AX-positive DNA damage. The results indicate that reduced oxidative stress, coupled with efficient but not error-free DNA damage repair, allows unscheduled long-term survival of genotoxin-exposed Fhitdeficient hematopoietic stem cells carrying deleterious mutations. [Cancer Res 2008;68(10):3662-70]

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Section: Resultsmentioning

confidence: 90%

Fhit-Deficient Hematopoietic Stem Cells Survive Hydroquinone Exposure Carrying Precancerous Changes

Ishii¹,

Mimori²,

Ishikawa³

et al. 2008

Cancer Research

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“…Benzene metabolites can sensitize the immune system as haptens to induce allergic response through suppressing NFKB binding activity . They also can interfere with immune responses by inhibiting cytokine production (Ibuki and Goto, 2004). Hydroquinone, a reactive metabolite of benzene, was found to reduce macrophage-mediated immune responses (Lee et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in genes involved in innate immunity and susceptibility to benzene-induced hematotoxicity

et al. 2011

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Benzene, a recognized hematotoxicant and carcinogen, can damage the human immune system. We studied the association between single nucleotide polymorphisms (SNPs) in genes involved in innate immunity and benzene hematotoxicity in a cross-sectional study of workers exposed to benzene (250 workers and 140 controls). A total of 1,236 tag SNPs in 149 gene regions of six pathways were included in the analysis. Six gene regions were significant for their association with white blood cell (WBC) counts (MBP, VCAM1, ALOX5, MPO, RAC2, and CRP) based on gene-region (P ＜ 0.05) and SNP analyses (FDR ＜0.05). VCAM1 rs3176867, ALOX5 rs7099684, and MPO rs2071409 were the three most significant SNPs. They showed similar effects on WBC subtypes, especially granulocytes, lymphocytes, and monocytes. A 3-SNP block in ALOXE3 (rs7215658, rs9892383, and rs3027208) showed a global association (omnibus P = 0.0008) with WBCs even though the three SNPs were not significant individually. Our study suggests that polymorphisms in innate immunity genes may play a role in benzene-induced hematotoxicity; however, independent replication is necessary.

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“…, responsáveis pelo estresse oxidativo e pela peroxidação lipídica (EASTMOND et al, 1987;THOMAS et al, 1990;KOLACHANA et al, 1993;ROSS et al, 1996;SHEN ET AL., 1996;IBUKI & GOTO, 2004;RANA & VERMA, 2005). Ainda, tem sido mostrado que a HQ altera o microambiente medular, com prejuízo na secreção e atividade de fatores de crescimento, entre os quais IL-1, interleucina 4 (IL-4), interleucina 12…”

Section: Efeitos Tóxicos Da Hidroquinonaunclassified

Efeitos da hidroquinona sobre atividades funcionais da célula endotelial e de neutrófilos

Pinedo¹

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Hydroquinone (HQ) is a fenolic compound obtained after benzene metabolism, it is a component of cigarette, medicines, photographic developer, and it is also finding in some foods and medicinal herbs. Our research group has been shown that rats in vivo exposed to HQ present impaired leukocyte migration into lung during allergic or non-specific inflammation. In the present study, we investigate the effects of HQ on functional activities of neutrophils and endothelial cells (EC) involved in inflammation. Primary cultured EC was obtained from microcirculatory network of maleWistar rats, and treated with HQ (10 or 100 µM, two hours). After the treatments, EC was incubated in presence or absence of lipopolissacharide of E. coli (LPS; 2 µg/mL). Peritoneal neutrophils obtained four hours after local injection of oyster glycogen (10 mL, 1%) were incubated with HQ (5 or 10 µM, one hour)

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Dysregulation of apoptosis by benzene metabolites and their relationships with carcinogenesis

Cited by 3 publications

References 0 publications

Fhit-Deficient Hematopoietic Stem Cells Survive Hydroquinone Exposure Carrying Precancerous Changes

Fhit-Deficient Hematopoietic Stem Cells Survive Hydroquinone Exposure Carrying Precancerous Changes

Polymorphisms in genes involved in innate immunity and susceptibility to benzene-induced hematotoxicity

Efeitos da hidroquinona sobre atividades funcionais da célula endotelial e de neutrófilos

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