Comparison of the biotransformation of 1,3-butadiene and its metabolite, butadiene monoepoxide, by hepatic and pulmonary tissues from humans, rats and mice.

Abstract:

:1,3-Butadiene (BD), a widely used monomer in the production of synthetic rubber and other resins, is one of the 189 hazardous air pollutants identified in the 1990 Clean Air Act Amendments. BD induces tumors at multiple organ sites in B6C3F1 mice and Sprague-Dawley rats; mice are much more susceptible to the carcinogenic action of BD than are rats. Previous in vivo studies have indicated higher circulating blood levels of butadiene monoepoxide (BMO), a potential carcinogenic metabolite of BD, in mice compared to rats, suggesting that species differences in the metabolism of BD may be responsible for the observed differences in carcinogenic susceptibility. The metabolic fate of BD in humans is unknown. The objective of these studies was to quantitate in vitro species differences in the oxidation of BD and BMO by cytochrome P450-dependent monooxygenases and the inactivation of BMO by epoxide hydrolases and glutathione S-transferases using microsomal and cytosolic preparations of livers and lungs obtained from Sprague-Dawley rats, B6C3F1 mice and humans. Maximum rates for BD oxidation (Vmax) were highest for mouse liver microsomes (2.6 nmol/mg protein/min) compared to humans (1.2) and rats (0.6). The Vmax for BD oxidation by mouse lung microsomes was similar to that of mouse liver but greater than 10-fold higher than the Vmax for the reaction in human or rat lung microsomes. Correlation analysis revealed that P450 2E1 is the major P450 enzyme responsible for oxidation of BD to BMO. Only mouse liver microsomes displayed quantifiable rates for metabolism of BMO to butadiene diepoxide (Vmax = 0.2 nmol/mg protein/min), a known rodent carcinogen. Human liver microsomes displayed the highest rate of BMO hydrolysis by epoxide hydrolases. The Vmax in human liver microsomes ranged from 9 to 58 nmol/mg protein/min and was at least 2-fold higher than the Vmax observed in mouse and rat liver microsomes. The Vmax for glutathione S-transferase-catalyzed conjugation of BMO with glutathione was highest for mouse liver cytosol (500 nmol/mg protein/min) compared to human (45) or rat (241) liver cytosol. In general, the KMs for the detoxication reactions were 1000-fold higher than the KMs for the oxidation reaction. Because of the low solubility of the BD and the relatively high KM for oxidation, it is likely that the Vmax/KM ratio will be important for BD and BMO metabolism in vivo. In vivo clearance constants were calculated from in vitro data for BD oxidation and BMO oxidation, hydrolysis and GSH conjugation.(ABSTRACT TRUNCATED AT 400 WORDS)

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Csanády GA,Guengerich FP,Bond JA

doi

10.1093/carcin/13.7.1143

keywords:

subject

Has Abstract

pub_date

1992-07-01 00:00:00

pages

1143-53

issue

7

eissn

0143-3334

issn

1460-2180

journal_volume

13

pub_type

杂志文章
  • Metabolism of benzo[a]pyrene in primary cultures of human hepatocytes: dose-response over a four-log range.

    abstract::Cultures of isolated human hepatocytes from three different human liver specimens were exposed for 24 h to media containing [3H]benzo[a]pyrene (BP) (0.1, 1.0, 10, 100 microM). The cells and media were harvested and extracted. Subsequent incubations of the aqueous phase with beta-glucuronidase and aryl sulfatase, follo...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/8.7.983

    authors: Monteith DK,Novotny A,Michalopoulos G,Strom SC

    更新日期:1987-07-01 00:00:00

  • Multistage chemical carcinogenesis protocols produce spindle cell carcinomas of the mouse skin.

    abstract::Spindle cell carcinomas were identified using polyacrylamide gel electrophoresis and immunoblotting of proteins extracted from paraffin-embedded tissue sections. Immunohistochemistry using rabbit monospecific antisera against the mouse 55 kd keratin polypeptide also identified these tumors. A group of 53 SENCAR mice i...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/10.11.2169

    authors: Klein-Szanto AJ,Larcher F,Bonfil RD,Conti CJ

    更新日期:1989-11-01 00:00:00

  • Exosomal miRNAs are potential diagnostic biomarkers between malignant and benign thyroid nodules based on next-generation sequencing.

    abstract::An accurate biomarker or method for diagnosis of thyroid nodule with indeterminate fine-needle aspiration result is essential for clinical treatment. Micro RNAs (miRNAs) of exosomes are advantageous in the diagnosis of tumors because they are highly stable, and be protected by a bilayer membrane structure. Exosomes we...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgz160

    authors: Pan Q,Zhao J,Li M,Liu X,Xu Y,Li W,Wu S,Su Z

    更新日期:2020-03-13 00:00:00

  • Apoptosis by dietary factors: the suicide solution for delaying cancer growth.

    abstract::Apoptosis, a form of programmed cell death, plays a fundamental role in the maintenance of tissues and organ systems by providing a controlled cell deletion to balanced cell proliferation. The last decade has witnessed an exponential increase in the number of studies investigating how different components of the diet ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章,评审

    doi:10.1093/carcin/bgl243

    authors: Khan N,Afaq F,Mukhtar H

    更新日期:2007-02-01 00:00:00

  • Discrimination of mutagenic intermediates derived from alkylating agents by mutational patterns generated in Escherichia coli.

    abstract::Reactive intermediates (ultimate mutagens/carcinogens) generated by alkylating agents are unstable and difficult to characterize by chemical means. We have used a genetic system to distinguish the in vivo interactions of eight carcinogenic methylating agents and five ethylating agents by the patterns of induced mutati...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/12.7.1161

    authors: Elespuru RK,Stupar LL,Gordon JA

    更新日期:1991-07-01 00:00:00

  • Identification and mutagenicity of metabolites of aristolochic acid formed by rat liver.

    abstract::The rat liver 9000 g supernatant mediated metabolism of the carcinogenic aristolochic acid, which consists of aristolochic acid I (AAI) and aristolochic acid II (AAII), was investigated. Under anaerobic conditions the major metabolites were the corresponding aristolactams for both AAI and AAII. In contrast under aerob...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/7.1.59

    authors: Schmeiser HH,Pool BL,Wiessler M

    更新日期:1986-01-01 00:00:00

  • Two inhibitors of gap junctional intercellular communication, TPA and endosulfan: different effects on phosphorylation of connexin 43 in the rat liver epithelial cell line, IAR 20.

    abstract::The skin tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and the chlorinated insecticide, endosulfan, are two potent inhibitors of gap junctional intercellular communication. In the present study the effects of TPA and endosulfan on cell communication have been investigated in IAR 20 rat liver epithelial ce...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/15.6.1161

    authors: Kenne K,Fransson-Steen R,Honkasalo S,Wärngård L

    更新日期:1994-06-01 00:00:00

  • Induction, repair and accumulation of thymine dimers in the skin of UV-B-irradiated hairless mice.

    abstract::A monoclonal antibody specific for cyclobutane thymine dimers in DNA was used in immunofluorescence studies to detect these lesions in skin sections taken from hairless mice that had been irradiated with UV-B. The dimer-specific fluorescence in epidermal cell nuclei was quantified with fluorescence microscopy through ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/12.5.861

    authors: Vink AA,Berg RJ,de Gruijl FR,Roza L,Baan RA

    更新日期:1991-05-01 00:00:00

  • Coffee consumption and risk of prostate cancer: a meta-analysis of prospective cohort studies.

    abstract::Observational studies and animal evidence suggest an association between coffee consumption and the risk of prostate cancer. However, the results are inconsistent. We evaluated the association by conducting a meta-analysis of prospective cohort studies. PubMed and Embase were searched through June 2013 to identify stu...

    journal_title:Carcinogenesis

    pub_type: 杂志文章,评审

    doi:10.1093/carcin/bgt482

    authors: Cao S,Liu L,Yin X,Wang Y,Liu J,Lu Z

    更新日期:2014-02-01 00:00:00

  • Restoration of preferential and strand specific gene repair in group 2 Chinese hamster ovary mutants (UV5) by the XPD (ERCC2) gene.

    abstract::It has recently been reported that the XPD (ERCC2) gene is an integral component of the basal transcription factor TFIIH. We have studied the direct role of this repair gene on the fine structure of DNA repair in hamster cells. The gene and strand specific DNA repair of UV induced pyrimidine dimers was determined in w...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/18.4.681

    authors: Cullinane C,Weber CA,Dianov G,Bohr VA

    更新日期:1997-04-01 00:00:00

  • Arsenite and cadmium promote the development of mammary tumors.

    abstract::Previous studies demonstrate that the heavy metal cadmium and the metalloid arsenite activate estrogen receptor-alpha in breast cancer cells by forming a high-affinity complex with the ligand-binding domain of the receptor and that environmentally relevant doses of cadmium have estrogen-like activity in vivo. The pres...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgz176

    authors: Divekar SD,Li HH,Parodi DA,Ghafouri TB,Chen R,Cyrus K,Foxworth AE,Fornace AJ,Byrne C,Martin MB

    更新日期:2020-07-14 00:00:00

  • Comparison of mutagenesis by O6-methyl- and O6-ethylguanine and O4-methylthymine in Escherichia coli using double-stranded and gapped plasmids.

    abstract::To compare mutagenesis by O6-methylguanine (m6G), O4-methylthymine (m4T) and O6-ethylguanine (e6G), and assess their genotoxicity in Escherichia coli, double-stranded and gapped plasmids were constructed containing a single m6G, e6G or m4T in the initiation codon (ATG) of a lacZ' gene. Modified base induced mutations ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/19.3.457

    authors: Pauly GT,Hughes SH,Moschel RC

    更新日期:1998-03-01 00:00:00

  • Prevention of liver carcinogenesis by amarogentin through modulation of G1/S cell cycle check point and induction of apoptosis.

    abstract::Amarogentin, a secoiridoid glycoside, is an active component of the medicinal plant Swertia chirata. In this study, chemopreventive and chemotherapeutic actions of amarogentin were evaluated in a carbon tetrachloride (CCl(4))/N-nitrosodiethylamine (NDEA)-induced liver carcinogenesis mouse model system during continuou...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgs276

    authors: Pal D,Sur S,Mandal S,Das A,Roy A,Das S,Panda CK

    更新日期:2012-12-01 00:00:00

  • Cancer stemness in Wnt-driven mammary tumorigenesis.

    abstract::Wnt signaling plays a central role in mammary stem cell (MaSC) homeostasis and in breast cancer. In particular, epigenetic alterations at different members of the Wnt pathway have been identified among triple-negative, basal-like breast cancers. Previously, we developed a mouse model for metaplastic breast adenocarcin...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgt279

    authors: Monteiro J,Gaspar C,Richer W,Franken PF,Sacchetti A,Joosten R,Idali A,Brandao J,Decraene C,Fodde R

    更新日期:2014-01-01 00:00:00

  • T cell status influences colon tumor occurrence in min mice fed short chain fructo-oligosaccharides as a diet supplement.

    abstract::We have previously shown that addition of short chain fructo-oligosaccharides (indigestible carbohydrates) to food prevented colon tumors in C57BL/6-Apc(Min/+) mice, a model for human colon cancer. As gut-associated lymphoid tissue was concomitantly developed, we suggested that the immune response generated by this fo...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/20.10.1953

    authors: Pierre F,Perrin P,Bassonga E,Bornet F,Meflah K,Menanteau J

    更新日期:1999-10-01 00:00:00

  • EGF promotes neuroendocrine-like differentiation of prostate cancer cells in the presence of LY294002 through increased ErbB2 expression independent of the phosphatidylinositol 3-kinase-AKT pathway.

    abstract::An increased neuroendocrine (NE) cell population in prostate cancer is associated with more aggressive disease and recurrence after androgen-deprivation therapy, although the mechanism responsible is unknown. In this study, we report that the treatment of LNCaP cells with epidermal growth factor (EGF) in the presence ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgs139

    authors: Cortés MA,Cariaga-Martinez AE,Lobo MV,Martín Orozco RM,Motiño O,Rodríguez-Ubreva FJ,Angulo J,López-Ruiz P,Colás B

    更新日期:2012-06-01 00:00:00

  • Interaction between functional polymorphic variants in cytokine genes, established risk factors and susceptibility to basal cell carcinoma of skin.

    abstract::Basal cell carcinoma (BCC) of the skin is the most common neoplasm among the Caucasian population of the Western world. Inflammation may result in oxidative stress and contribute to promotion and progression of tumors, including BCC. The role of cytokines, which are inflammatory modulators, in the biology of tumors ha...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgr197

    authors: Rizzato C,Canzian F,Rudnai P,Gurzau E,Stein A,Koppova K,Hemminki K,Kumar R,Campa D

    更新日期:2011-12-01 00:00:00

  • Highly purified human alpha-thrombin promotes morphological transformation of BALB/c 3T3 cells.

    abstract::Purified human alpha-thrombin stimulates phosphoinositide turnover as a necessary step in its stimulation of fibroblast cell proliferation. Since phosphoinositide turnover releases diacylglycerol, which activates protein kinase C, we postulated that long-term exposure to thrombin might promote cellular transformation ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/13.1.1

    authors: Morris DL,Ward JB Jr,Nechay P,Whorton EB Jr,Fenton JW 2nd,Carney DH

    更新日期:1992-01-01 00:00:00

  • Bioactivation of 2-nitrofluorene to reactive intermediates that bind covalently to DNA, RNA and protein in vitro and in vivo in the rat.

    abstract::The activation of 2-nitrofluorene (2-NF) to reactive intermediates that bind covalently to DNA, RNA and protein has been investigated both in vitro and in the rat in vivo. In vitro, such binding was catalyzed by the hepatic microsomal fraction, was NADPH dependent and could be inhibited by SKF 525A, an inhibitor of cy...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/11.1.27

    authors: Wierckx FC,Wedzinga R,Meerman JH,Mulder GJ

    更新日期:1990-01-01 00:00:00

  • Tissue distribution and macromolecular binding of extremely low doses of [14C]-benzene in B6C3F1 mice.

    abstract::The tissue distribution and macromolecular binding of benzene was studied over a dose range spanning nine-orders of magnitude to determine the nature of the dose-response and to establish benzene's internal dosimetry at doses encompassing human environmental exposures. [14C]-Benzene was administered to B6C3F1 male mic...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/18.12.2421

    authors: Creek MR,Mani C,Vogel JS,Turteltaub KW

    更新日期:1997-12-01 00:00:00

  • Increased susceptibility to oxidative DNA damage in regenerating liver.

    abstract::Spontaneous and hepatocarcinogen (2-nitropropane, 2-NP)-induced levels of 8-hydroxy-2'-deoxyguanosine (oh8dG) in the nuclear DNA of regenerating liver [24, 48, 72 h and 7 days after partial hepatectomy (PH)] of male Sprague-Dawley rats were analysed for the verification of a hypothesis that the high susceptibility of ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/15.3.539

    authors: Adachi S,Kawamura K,Takemoto K

    更新日期:1994-03-01 00:00:00

  • Chemoprevention of inflammation-related colorectal cancer by silymarin-, acetyl-11-keto-beta-boswellic acid-, curcumin- and maltodextrin-enriched dietetic formulation in animal model.

    abstract::On the basis of preliminary in vitro experience, we assessed whether an enriched nutritional formulation with estrogen receptor (ER)-beta agonist and anti-inflammatory properties may prevent inflammation-associated colorectal cancer (CRC) in an animal model. Study sample enclosed 110 C57BL/6J male mice. Forty underwen...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgy104

    authors: Girardi B,Principi M,Pricci M,Giorgio F,Iannone A,Losurdo G,Ierardi E,Di Leo A,Barone M

    更新日期:2018-10-08 00:00:00

  • Strong anti-mutagenic activity of the novel lipophilic antioxidant 1-O-hexyl-2,3,5-trimethylhydroquinone against heterocyclic amine-induced mutagenesis in the Ames assay and its effect on metabolic activation of 2-amino-6-methyldipyrido[1,2-a:3',2'-d] imi

    abstract::Antimutagenic effects of a novel lipophilic antioxidant, 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ), and other known antioxidants against heterocyclic amine- or other mutagen-induced mutagenesis were examined in the Ames assay using Salmonella strain TA 98 to access the chemo-preventive effects of antioxidants on he...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/16.9.2227

    authors: Hirose M,Iwata S,Ito E,Nihro Y,Takahashi S,Mizoguchi Y,Miki T,Satoh T,Ito N,Shirai T

    更新日期:1995-09-01 00:00:00

  • Hypoxia and nickel inhibit histone demethylase JMJD1A and repress Spry2 expression in human bronchial epithelial BEAS-2B cells.

    abstract::Epigenetic silencing of tumor suppressor genes commonly occurs in human cancers via increasing DNA methylation and repressive histone modifications at gene promoters. However, little is known about how pathogenic environmental factors contribute to cancer development by affecting epigenetic regulatory mechanisms. Prev...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgq197

    authors: Chen H,Kluz T,Zhang R,Costa M

    更新日期:2010-12-01 00:00:00

  • Changes in methyl-sensitive restriction sites of liver DNA from hamsters chronically exposed to hydrazine sulfate.

    abstract::Hydrazine sulfate is a genotoxic hepatocarcinogen for the hamster. A study was conducted to follow changes in DNA maintenance methylation in selected genes in liver DNA during the 21-month induction of liver adenomas and hepatocellular carcinomas by demonstrating changes in restriction fragment length polymorphism. Ma...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/17.12.2711

    authors: Zheng H,Shank RC

    更新日期:1996-12-01 00:00:00

  • RSK2 as a key regulator in human skin cancer.

    abstract::Our previous report demonstrated that RSK2 plays an important role in cell proliferation and transformation induced by tumor promoters such as epidermal growth factor mediated through the N-terminal kinase domain of RSK2 in JB6 Cl41 mouse skin epidermal cells in vitro. However, no direct evidence has been reported reg...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgs271

    authors: Cho YY,Lee MH,Lee CJ,Yao K,Lee HS,Bode AM,Dong Z

    更新日期:2012-12-01 00:00:00

  • Herbacetin suppresses cutaneous squamous cell carcinoma and melanoma cell growth by targeting AKT and ODC.

    abstract::Herbacetin is a flavonol compound that is found in plants such as flaxseed and ramose scouring rush herb, it possesses a strong antioxidant capacity, and exerts anticancer effects on colon and breast cancer. However, the effect of herbacetin on skin cancer has not been investigated. Herein, we identified herbacetin as...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgx082

    authors: Kim DJ,Lee MH,Liu K,Lim DY,Roh E,Chen H,Kim SH,Shim JH,Kim MO,Li W,Ma F,Fredimoses M,Bode AM,Dong Z

    更新日期:2017-10-26 00:00:00

  • 32P-postlabeling analysis of liver DNA adducts in rats chronically fed a choline-devoid diet.

    abstract::Liver DNA, obtained at various time intervals from rats chronically fed a choline-devoid diet, was analysed for the presence of aromatic or alkyl adducts by the 32P-postlabeling assay. Alkyl adducts were not detected. Aromatic DNA adduct lesions were revealed, but only at levels (1 adduct per 0.5-3 X 10(9) nucleotides...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/8.1.187

    authors: Gupta RC,Earley K,Locker J,Lombardi B

    更新日期:1987-01-01 00:00:00

  • The global burden of cancer: priorities for prevention.

    abstract::Despite decreases in the cancer death rates in high-resource countries, such as the USA, the number of cancer cases and deaths is projected to more than double worldwide over the next 20-40 years. Cancer is now the third leading cause of death, with >12 million new cases and 7.6 million cancer deaths estimated to have...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgp263

    authors: Thun MJ,DeLancey JO,Center MM,Jemal A,Ward EM

    更新日期:2010-01-01 00:00:00

  • Associations of dietary methyl donor intake with MLH1 promoter hypermethylation and related molecular phenotypes in sporadic colorectal cancer.

    abstract::Intake of dietary factors that serve as methyl group donors may influence promoter hypermethylation in colorectal carcinogenesis. We investigated whether dietary folate, vitamin B2 and vitamin B6, methionine and alcohol were associated with mutL homologue 1 (MLH1) hypermethylation and the related molecular phenotypes ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgn074

    authors: de Vogel S,Bongaerts BW,Wouters KA,Kester AD,Schouten LJ,de Goeij AF,de Bruïne AP,Goldbohm RA,van den Brandt PA,van Engeland M,Weijenberg MP

    更新日期:2008-09-01 00:00:00