Benzene, the exposome and future investigations of leukemia etiology.


:Benzene exposure is associated with acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and probably lymphoma and childhood leukemia. Biological plausibility for a causal role of benzene in these diseases comes from its toxicity to hematopoietic stem cells (HSC) or progenitor cells, from which all leukemias and related disorders arise. The effect of this toxicity is manifest as lowered blood counts (hematotoxicity), even in individuals occupationally exposed to low levels of benzene. Benzene can induce AML/MDS via several well-characterized pathways associated with these diseases. Through its metabolites, benzene induces multiple alterations that likely contribute to the leukemogenic process, and appears to operate via multiple modes of action. To improve mechanistic understanding and for risk assessment purposes, it may be possible to measure several of the key events in these modes of action in an in vitro model of the bone marrow stem cell niche. Even though benzene is leukemogenic at relatively low occupational levels of exposure, it seems unlikely that it is a major cause of leukemia in the general population exposed to benzene in the ppb range. Other established non-genetic causes of AML, e.g. smoking, ionizing radiation and cancer chemotherapy, also only explain about 20% of AML incidence, leaving ∼80% unexplained. The question arises as to how to find the causes of the majority of de novo AMLs that remain unexplained. We propose that we should attempt to characterize the 'exposome' of human leukemia by using unbiased laboratory-based methods to find the unknown 'environmental' factors that contribute to leukemia etiology.


Chem Biol Interact


Smith MT,Zhang L,McHale CM,Skibola CF,Rappaport SM




Has Abstract


2011-06-30 00:00:00














  • Studies on the relationship between dimethylnitrosamine-demethylase activity and dimethylnitrosamine-dependent mutagenesis in Drosophila melanogaster.

    abstract::The relationship between dimethylnitrosamine (DMN) demethylase activity and DMN-induced mutagenesis was investigated in Drosophila melanogaster. The activity of DMN-demethylase was at least 10-fold greater in the Hikone-R strain than in three other Drosophila strains. However, the sex-linked recessive lethal (SLRL) mu...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Waters LC,Nix CE,Epler JL

    更新日期:1983-08-15 00:00:00

  • Effects of peroxisome proliferators and/or hypothyroidism on xenobiotic-metabolizing enzymes in rat testis.

    abstract::The objectives of the present work were to study the effects of certain peroxisome proliferators on xenobiotic-metabolizing enzyme activities in the testes of normal and hypothyroid rats, i.e. phenol sulfotransferases (pST), phenol UDP-glucuronosyl transferases (pUDPGT), glutathione transferases (GST), catalase, epoxi...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Mehrotra K,Morgenstern R,Lundqvist G,Becedas L,Bengtsson Ahlberg M,Georgellis A

    更新日期:1997-05-02 00:00:00

  • pH effects on the N-demethylation and formation of the cytochrome P-450 iron II nitrosoalkane complex for erythromycin derivatives.

    abstract::The effects of pH on access to the cytochrome P-450 active site, N-demethylation and formation of the cytochrome P-450 Fe(II)-RNO metabolite complex for a series of erythromycin derivatives were examined. Studies were performed with dexamethasone-treated rat liver microsomes containing large amounts of cytochrome P-45...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Delaforge M,Ladam P,Bouillé G,Benarous JG,Jaouen M,Girault JP

    更新日期:1992-12-01 00:00:00

  • Induction of apoptosis in K562/ADM cells by gamma-linolenic acid involves lipid peroxidation and activation of caspase-3.

    abstract::Numerous studies have revealed that gamma-linolenic acid (GLA) possesses effective tumoricidal properties while not inducing damage to normal cells or creating harmful systemic side effects. It can exert anti-tumor efficacy against a variety of cancers including leukemia. However, little is known about the effects of ...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Kong X,Ge H,Hou L,Shi L,Liu Z

    更新日期:2006-08-25 00:00:00

  • Methylation of DNA in rat liver and intestine by dimethylnitrosamine and N-methylnitrosourea.

    abstract::A chromatographic procedure for improved separation of deoxyribonucleosides and methylated deoxyribonucleosides is described. DNA was isolated from liver and small intestine of rats treated with [14C]dimethylnitrosamine ([14C]DMN) or N-[3H]methyl-N-nitrosourea ([3H]MNU), and the purified DNA was hydrolyzed enzymatical...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Daoud AH,Irving CC

    更新日期:1977-02-01 00:00:00

  • Interaction of benzo [A] pyrene and a hyperplastic agent in epidermal nuclear enlargement in the mouse. A dose response study.

    abstract::Experiments were conducted on the effects of various dose levels of benzo [a]pyrene (BP) on nuclear size in mouse interfollicular epidermis over a 3-day period. Topical application of BP was made with or without croton oil (CO) (0.1 or 0.5%) in the vehicles acetone, toluene and methyl ethyl ketone (MEK). Nuclear size ...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Ingram AJ

    更新日期:1979-06-01 00:00:00

  • CRKL promotes cell proliferation in gastric cancer and is negatively regulated by miR-126.

    abstract::V-crk avian sarcoma virus CT10 oncogene homolog-like (CRKL) is a member of CRK family and act as an adaptor protein participating in intra-cellular signal transduction. The role of CRKL in gastric cancer (GC) remains unclear. In this study, we show that CRKL was aberrantly highly expressed in both GC tumor specimens a...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Wang J,Chen X,Li P,Su L,Yu B,Cai Q,Li J,Yu Y,Liu B,Zhu Z

    更新日期:2013-11-25 00:00:00

  • Interaction of DNA with water soluble complex of Nickle and formation of DNA cross-links.

    abstract::Interaction of double stranded DNA with bulky and hydrophobic Salen type Schiff base complex: [N, N' Bis [3- tert-butyl-5-[triphenyl-phosphonium - methyl] - salicylidene] 1,2 ethylene-diamine nickel(III) acetate (refer to Ni Salen complex) was extensively investigated using the spectroscopic techniques and gel electro...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Nejat Dehkordi M,Akerman B

    更新日期:2018-02-25 00:00:00

  • Influence of pH on the reactivity of diphenyl ditelluride with thiols and anti-oxidant potential in rat brain.

    abstract::Thiol oxidation by diphenyl ditelluride is a favorable reaction and may be responsible for alteration in regulatory or signaling pathways. We have measured rate constants for reactions of diphenyl ditelluride with cysteine, dimercaptosuccinic acid, glutathione and dithiothreitol in phosphate buffer. The relative react...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Hassan W,Ibrahim M,Nogueira CW,Braga AL,Deobald AM,Mohammadzai IU,Rocha JB

    更新日期:2009-06-15 00:00:00

  • Signal transduction mechanism in response to aflatoxin B1 exposure: protein kinase C activity.

    abstract::A single dose of the carcinogen aflatoxin B1 (7 mg/kg body weight) to male Wistar rats significantly enhanced the hepatic activity of protein kinase C in the particulate and nuclear fractions. The particulate fraction showed stimulation at 4 and 7 h, while the nuclear activity was increased at 17 h following administr...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


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    更新日期:1996-03-25 00:00:00

  • Mechanism of unbalanced growth-induced cell damage. I. A probable role for hydrolytic enzymes synthesis.

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    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


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    更新日期:1986-03-01 00:00:00

  • Concentration-dependent inhibitory effects of baicalin on the metabolism of dextromethorphan, a dual probe of CYP2D and CYP3A, in rats.

    abstract::Baicalin has been shown to possess many pharmacological effects, including antiviral, antioxidant, anti-cancer and anti-inflammatory properties. In the current study, we reveal the inhibitory effects of baicalin on the metabolism of dextromethorphan (DXM), a dual probe substrate of CYP2D and CYP3A, in rats. Lineweaver...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Tian X,Cheng ZY,He J,Jia LJ,Qiao HL

    更新日期:2013-04-25 00:00:00

  • Hyposensitivity to the amnesic effects of scopolamine or amyloid beta(25-35) peptide in heterozygous acetylcholinesterase knockout (AChE(+/-)) mice.

    abstract::We examined the sensitivity of AChE(+/-) mice to the amnesic effects of scopolamine and amyloid beta peptide. AChE(+/-) and AChE(+/+) littermates, tested at 5-9 weeks of age, failed to show any difference in locomotion, exploration and anxiety in the open-field test, or in-place learning in the water-maze. However, wh...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Espallergues J,Galvan L,Lepourry L,Bonafos B,Maurice T,Chatonnet A

    更新日期:2008-09-25 00:00:00

  • The metabolic activation of abacavir by human liver cytosol and expressed human alcohol dehydrogenase isozymes.

    abstract::Abacavir (ZIAGEN) is a reverse transcriptase inhibitor marketed for the treatment of HIV-1 infection. A small percentage of patients experience a hypersensitivity reaction indicating immune system involvement and bioactivation. A major route of metabolism for abacavir is oxidation of a primary betagamma unsaturated al...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Walsh JS,Reese MJ,Thurmond LM

    更新日期:2002-11-10 00:00:00

  • A map of the PPARα transcription regulatory network for primary human hepatocytes.

    abstract::Nuclear receptor activation in liver leads to coordinated alteration of the expression of multiple gene products with attendant phenotypic changes of hepatocytes. Peroxisome proliferators including endogenous fatty acids, environmental chemicals, and drugs induce a multi-enzyme metabolic response that affects lipid an...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: McMullen PD,Bhattacharya S,Woods CG,Sun B,Yarborough K,Ross SM,Miller ME,McBride MT,LeCluyse EL,Clewell RA,Andersen ME

    更新日期:2014-02-25 00:00:00

  • Mode of in vitro interaction of mercuric mercury with selenite to form high-molecular weight substance in rabbit blood.

    abstract::Mode of interaction of mercuric mercury and selenite in rabbit blood was investigated in vitro. After the incubation of rabbit blood with 10(-5) M each of 203HgCl2 and Na2(75)SeO3, the amounts of both 203Hg and 75Se incorporated into erythrocytes were markedly larger than the case where the blood was treated separatel...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


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    更新日期:1983-03-01 00:00:00

  • Comparative excretion and tissue distribution of selenium in mice and rats following treatment with the chemopreventive agent 1,4-phenylenebis(methylene)selenocyanate.

    abstract::In a previous preliminary investigation, we reported on the excretion, tissue disposition and metabolism of the chemopreventive agent 1,4-phenylenebis(methylene)selenocyanate (p-XSC) in the rat, but similar studies in the mouse have not been explored. Following the oral administration of p-XSC (50 micromol/kg body wei...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Sohn OS,Desai DH,Das A,Rodriguez JG,Amin SG,El-Bayoumy K

    更新日期:2005-02-10 00:00:00

  • Studies on the reduction of nitroblue tetrazolium chloride mediated through the action of NADH and phenazine methosulphate.

    abstract::The general features of the reduction of nitroblue tetrazolium chloride (NBT) by NADH and phenazine methosulphate (PMS) have been studied under aerobic and anaerobic conditions. Under aerobic condition the reduction appears to be mediated through the intermediate formation of the superoxide anion radical O2-.; this re...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Ponti V,Dianzani MU,Cheeseman K,Slater TF

    更新日期:1978-12-01 00:00:00

  • Potential implication of aniline derivatives in the Toxic Oil Syndrome (TOS).

    abstract::The Toxic Oil Syndrome (TOS) was an epidemic disease appeared in central Spain in 1981, causing over 400 deaths and affecting more than 20,000 people, mainly women and children. The disease was linked to the consumption of rapeseed oil denatured with aniline, illegally refined at the ITH oil refinery in Seville, mixed...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Messeguer A

    更新日期:2011-06-30 00:00:00

  • Redox cycling of polycyclic aromatic hydrocarbon o-quinones: metal ion-catalyzed oxidation of catechols bypasses inhibition by superoxide dismutase.

    abstract::Several two-electron quinone reductases catalyze the redox cycling of polycyclic aromatic hydrocarbon (PAH) o-quinones. When the carbonyl reductase of human placenta catalyzes the cycling of 9,10-phenanthrenequinone in aqueous phosphate buffer, reactive oxygen species are produced. Superoxide dismutase (SOD) inhibits ...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Jarabak R,Harvey RG,Jarabak J

    更新日期:1998-10-02 00:00:00

  • Human and murine steroid 5β-reductases (AKR1D1 and AKR1D4): insights into the role of the catalytic glutamic acid.

    abstract::Mammalian steroid 5β-reductases belong to the Aldo-Keto Reductase 1D sub-family and are essential for the formation of A-ring 5β-reduced steroids. Steroid 5β-reduction is required for the biosynthesis of bile-acids and the metabolism of all steroid hormones that contain a Δ4-3-ketosteroid functionally to yield the 5β-...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Chen M,Wangtrakuldee P,Zang T,Duan L,Gathercole LL,Tomlinson JW,Penning TM

    更新日期:2019-05-25 00:00:00

  • Joint toxic effects of the type-2 alkene electrophiles.

    abstract::Human populations are exposed to complex environmental mixtures of acrolein, methylvinyl ketone (MVK) and other type-2 alkenes. Many members of this chemical class are electrophiles that possess a common molecular mechanism of toxicity; i.e., protein inactivation via formation of stable cysteine adducts. Therefore, ac...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Zhang L,Geohagen BC,Gavin T,LoPachin RM

    更新日期:2016-07-25 00:00:00

  • Anti-inflammatory effects of dabrafenib on polyphosphate-mediated vascular disruption.

    abstract::The screening of bioactive compound libraries can be an effective approach for repositioning FDA-approved drugs or discovering new treatments for human diseases. Previous studies have reported polyphosphate (PolyP)-mediated vascular inflammatory responses such as disruption of vascular integrity. Dabrafenib is a B-Raf...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Lee S,Ku SK,Bae JS

    更新日期:2016-08-25 00:00:00

  • Impact of diet on irinotecan toxicity in mice.

    abstract::Irinotecan is highly effective in the treatment of metastatic colorectal cancer as well as many other cancers. However, irinotecan is known to cause severe diarrhea, which pose significant problems in patients undergoing irinotecan based chemotherapy. Dietary and herbal components have shown promise in improving gastr...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Mallick P,Shah P,Ittmann MM,Trivedi M,Hu M,Gao S,Ghose R

    更新日期:2018-08-01 00:00:00

  • The effect of disease associated point mutations on 5β-reductase (AKR1D1) enzyme function.

    abstract::The stereospecific 5β-reduction of Δ(4)-3-ketosterols is very difficult to achieve chemically and introduces a 90° bend between ring A and B of the planar steroid. In mammals, the reaction is catalyzed by steroid 5β-reductase, a member of the aldo-keto reductase (AKR) family. The human enzyme, AKR1D1, plays an essenti...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章,meta分析


    authors: Mindnich R,Drury JE,Penning TM

    更新日期:2011-05-30 00:00:00

  • Chemical features of flavonols affecting their genotoxicity. Potential implications in their use as therapeutical agents.

    abstract::Flavonls are natural compounds present in edible plants and possess several biological activities that can be useful in drug design. Conversely some of these compounds have been shown to be genotoxic to prokaryotic and eukaryotic cells. In this study we tried to establish the chemical features responsible for the geno...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Silva ID,Gaspar J,da Costa GG,Rodrigues AS,Laires A,Rueff J

    更新日期:2000-01-03 00:00:00

  • Lack of effect of glutathione depletion on cytotoxicity, mutagenicity and DNA damage produced by doxorubicin in cultured cells.

    abstract::Since endogenous glutathione (GSH), the main non-protein intracellular thiol compound, is known to provide protection against reactive radical species, its depletion by diethylmaleate (DEM) was used to assess the role of free radical formation mediated by doxorubicin in DNA damage, cytotoxicity and mutagenicity of the...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Capranico G,Babudri N,Casciarri G,Dolzani L,Gambetta RA,Longoni E,Pani B,Soranzo C,Zunino F

    更新日期:1986-02-01 00:00:00

  • The environmental pollutant and tobacco smoke constituent dibenzo[def,p]chrysene is a co-factor for malignant progression of mouse oral papillomavirus infections.

    abstract::HPV infections in the oral cavity that progress to cancer are on the increase in the USA. Model systems to study co-factors for progression of these infections are lacking as HPVs are species-restricted and cannot grow in preclinical animal models. We have recently developed a mouse papillomavirus (MmuPV1) oral mucosa...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Christensen ND,Chen KM,Hu J,Stairs DB,Sun YW,Aliaga C,Balogh KK,Atkins H,Shearer D,Li J,Brendle SA,Gowda K,Amin S,Walter V,Viscidi R,El-Bayoumy K

    更新日期:2021-01-05 00:00:00

  • Detailed analytical subcellular fractionation of non-pregnant porcine corpus luteum reveals peroxisomes of normal size and significant UDP-glucuronosyltransferase activity in the high-speed supernatant.

    abstract::A detailed subfractionation of the non-pregnant porcine corpus luteum (CL) was performed employing differential centrifugation. Marker enzyme assays (i.e., lactate dehydrogenase for the cytosol, NADPH-cytochrome P450 reductase for the endoplasmatic reticulum, catalase (CAT) for peroxisomes, glutamate dehydrogenase for...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Boström M,Björk K,Nelson BD,DePierre JW

    更新日期:2004-01-15 00:00:00

  • Sulfated polysaccharides from the edible marine algae Padina tetrastromatica attenuates isoproterenol-induced oxidative damage via activation of PI3K/Akt/Nrf2 signaling pathway - An in vitro and in vivo approach.

    abstract::The reactive oxygen species (ROS) induced oxidative stress is an inevitable factor for the pathogenesis of cardiovascular diseases. The edible marine algae-derived sulfated polysaccharides gained special attention as novel bioactive compounds having potential pharmacological activities. The present study evaluated in ...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: V S L,Rauf AA,Kurup GM

    更新日期:2019-08-01 00:00:00