Benzo(a)pyrene-induced cytotoxicity, cell proliferation, DNA damage, and altered gene expression profiles in HT-29 human colon cancer cells.

Abstract:

:In the US alone, around 60,000 lives/year are lost to colon cancer. In order to study the mechanisms of colon carcinogenesis, in vitro model systems are required in addition to in vivo models. Towards this end, we have used the HT-29 colon cancer cells, cultured in Dulbecco's Modified Eagle Medium (DMEM), which were exposed to benzo(a)pyrene (BaP), a ubiquitous and prototypical environmental and dietary toxicant at 1, 10, 100 nM and 1, 5, 10, and 25 μM concentrations for 96 h. Post-BaP exposure, growth, cytotoxicity, apoptosis, and cell cycle changes were determined. The BaP metabolite concentrations in colon cells were identified and measured. Furthermore, the BaP biotransformation enzymes were studied at the protein and mRNA levels. The BaP exposure-induced damage to DNA was assessed by measuring the oxidative damage to DNA and the concentrations of BaP-DNA adducts. To determine the whole repertoire of genes that are up- or downregulated by BaP exposure, mRNA transcriptome analysis was conducted. There was a BaP exposure concentration (dose)-dependent decrease in cell growth, cytotoxicity, and modulation of the cell cycle in the treatment groups compared to untreated or dimethylsulfoxide (DMSO: vehicle for BaP)-treated categories. The phase I biotransformation enzymes, CYP1A1 and 1B1, showed BaP concentration-dependent expression. On the other hand, phase II enzymes did not exhibit any marked variation. Consistent with the expression of phase I enzymes, elevated concentrations of BaP metabolites were generated, contributing to the formation of DNA lesions and stable DNA adducts, which were also BaP concentration-dependent. In summary, our studies established that biotransformation of BaP contributes to cytotoxicity, proliferation of tumor cells, and alteration of gene expression by BaP. • Benzo(a)pyrene (BaP) is an environmental and dietary toxicant. • BaP causes cytotoxicity in cultured HT-29 colon cancer cells. • mRNA transcriptome analyses revealed that BaP impacts cell growth, cell cycle, biotransformation, and DNA damage.

journal_name

Cell Biol Toxicol

authors

Myers JN,Harris KL,Rekhadevi PV,Pratap S,Ramesh A

doi

10.1007/s10565-020-09579-5

subject

Has Abstract

pub_date

2021-01-07 00:00:00

eissn

0742-2091

issn

1573-6822

pii

10.1007/s10565-020-09579-5

pub_type

杂志文章
  • Echinoderm regenerative response as a sensitive ecotoxicological test for the exposure to endocrine disrupters: effects of p,p'DDE and CPA on crinoid arm regeneration.

    abstract::Echinoderms are valuable test species in marine ecotoxicology and offer a wide range of biological processes appropriate for this approach. Regenerating echinoderms can be regarded as amenable experimental models for testing the effects of exposure to contaminants, particularly endocrine disrupter compounds (EDCs). As...

    journal_title:Cell biology and toxicology

    pub_type: 杂志文章

    doi:10.1007/s10565-008-9057-y

    authors: Sugni M,Manno V,Barbaglio A,Mozzi D,Bonasoro F,Tremolada P,Candia Carnevali MD

    更新日期:2008-12-01 00:00:00

  • The lack of genotoxicity of sodium fluoride in a battery of cellular tests.

    abstract::In a comprehensive assessment of genotoxicity, sodium fluoride was evaluated in a battery of cellular tests providing different genetic end points and biotransformation capabilities. The tests included the following: rat hepatocyte primary culture/DNA repair assay, Salmonella typhimurium histidine locus reversion assa...

    journal_title:Cell biology and toxicology

    pub_type: 杂志文章

    doi:10.1007/BF00119244

    authors: Tong CC,McQueen CA,Brat SV,Williams GM

    更新日期:1988-06-01 00:00:00

  • Quantitative evaluation of the effects of human carcinogens and related chemicals on human foreskin fibroblasts.

    abstract::Ten compounds representative of diverse classes of chemicals were evaluated for their cytotoxicity and transforming ability to human skin fibroblasts in vitro. Only five of the ten compounds were highly cytotoxic in the 0-100 micrograms/ml range and their order of cytotoxicity was: 2,5-bis(1-aziridinyl)-3,6-bis(carboe...

    journal_title:Cell biology and toxicology

    pub_type: 杂志文章

    doi:10.1007/BF00249592

    authors: Kurian P,Nesnow S,Milo GE

    更新日期:1990-04-01 00:00:00

  • Comparative microarray analyses of mono(2-ethylhexyl)phthalate impacts on fat cell bioenergetics and adipokine network.

    abstract::Cellular accumulation of mono(2-ethylhexyl)phthalate (MEHP) has been recently demonstrated to disturb fat cell energy metabolism; however, the underlying mechanism remained unclear. The study aimed to determine how MEHP influenced fat cell transcriptome and how the changes might contribute to bioenergetics. Because of...

    journal_title:Cell biology and toxicology

    pub_type: 杂志文章

    doi:10.1007/s10565-016-9380-7

    authors: Chiang HC,Wang CH,Yeh SC,Lin YH,Kuo YT,Liao CW,Tsai FY,Lin WY,Chuang WH,Tsou TC

    更新日期:2017-12-01 00:00:00

  • Effects of aplysiatoxin and debromoaplysiatoxin on growth and differentiation of normal human bronchial epithelial cells.

    abstract::The effects of aplysiatoxin and debromoaplysiatoxin on the clonal growth rate, cross-linked envelope formation and plasminogen activator secretion of normal human bronchial epithelial cells were studied. Neither compound was mitogenic over a wide range of concentrations (10(-13) to 10(-7)M). Both aplysiatoxin and debr...

    journal_title:Cell biology and toxicology

    pub_type: 杂志文章

    doi:10.1007/BF00125571

    authors: Willey JC,Moser CE Jr,Harris CC

    更新日期:1984-10-01 00:00:00

  • New approaches to estimating the mutagenic potential of chemicals.

    abstract::New developments in mutagenic risk assessment have appeared in the past few years. New methods have been developed such as in vitro micronucleus assay for chromosomal alterations, comet assay for primary DNA damage, use of transgenic animals to detect in vivo gene mutations, and fluorescent in situ hybridization metho...

    journal_title:Cell biology and toxicology

    pub_type: 杂志文章,评审

    doi:10.1023/a:1007697715084

    authors: Marzin D

    更新日期:1999-01-01 00:00:00

  • Environmentally relevant cadmium concentrations affect development and induce apoptosis of Paracentrotus lividus larvae cultured in vitro.

    abstract::Sea urchin embryos and larvae represent suitable model systems on where to investigate the effects of heavy metals on development and cell viability. Here, we tested the toxic effects of low (10(-12 )M), medium (10(-9 )M), and high (10(-6 )M) cadmium chloride concentrations, mimicking unpolluted, moderately and highly...

    journal_title:Cell biology and toxicology

    pub_type: 杂志文章

    doi:10.1007/s10565-008-9066-x

    authors: Filosto S,Roccheri MC,Bonaventura R,Matranga V

    更新日期:2008-12-01 00:00:00

  • Role of ErbB2 mediated AKT and MAPK pathway in gall bladder cell proliferation induced by argemone oil and butter yellow. Argemone oil and butter yellow induced gall bladder cell proliferation.

    abstract::The effect of noncytotoxic doses of argemone oil (AO) and butter yellow (BY), the common adulterants in edible oil, on free radical generation and signaling pathway for cell proliferation in primary cells of gall bladder (GB) was undertaken. AO and BY showed no cytotoxicity at 0.1 μl/ml and 0.1 μg/ml concentration, re...

    journal_title:Cell biology and toxicology

    pub_type: 杂志文章

    doi:10.1007/s10565-011-9207-5

    authors: Mishra V,Ansari KM,Khanna R,Das M

    更新日期:2012-06-01 00:00:00

  • Cocarcinogenesis in vitro using Balb/3T3 cells and aromatic hydrocarbon cocarcinogens.

    abstract::The mouse skin cocarcinogens fluoranthene, pyrene, and undecane were used with the indirect-acting carcinogen, benzo(a)pyrene (BP), and the direct-acting alkylating carcinogen, beta-propiolactone (BPL), in an in vitro transformation assay. Dose response, cytotoxicity, and transformation studies with these compounds we...

    journal_title:Cell biology and toxicology

    pub_type: 杂志文章

    doi:10.1007/BF00118197

    authors: Atchison M,Atchison ML,Van Duuren BL

    更新日期:1985-10-01 00:00:00

  • In vitro tolerability of human nasal mucosa: histopathological and scanning electron-microscopic evaluation of nasal forms containing Sandostatin.

    abstract::An in vitro human nasal model was developed as a tool to study the local tolerability of nasal powder forms using excised nasal mucosa in a diffusion chamber. The suitability of this model was tested using Sandostatin (SMS) an octapeptide analog of somatostatin, as a reference drug enhanced by Avicel (microcrystalline...

    journal_title:Cell biology and toxicology

    pub_type: 杂志文章

    doi:10.1007/BF00757627

    authors: de Fraissinette A,Kolopp M,Schiller I,Fricker G,Gammert C,Pospischil A,Vonderscher J,Richter F

    更新日期:1995-10-01 00:00:00

  • Two models for screening chelating agents for cadmium removal.

    abstract::The effectiveness of some chelating agents to mobilize cadmium from Chinese hamster ovary cells after chronic exposure (20 hr), as well as from cytosolic metallothionein, was studied. In the first protocol, the most effective substance was 2,3-dimercaptopropanol, followed by 2,3-dimercaptopropane-1-sulfonate and 2,3-d...

    journal_title:Cell biology and toxicology

    pub_type: 杂志文章

    doi:10.1007/BF00141067

    authors: Rau W,Planas-Bohne F,Taylor DM

    更新日期:1989-01-01 00:00:00

  • Cytotoxicity of sodium fluoride on human oral mucosal fibroblasts and its mechanisms.

    abstract::Because sodium fluoride (NaF) is widely used for prevention of dental caries, pathobiological effects of NaF were investigated on human oral mucosal fibroblasts. The results showed that NaF was cytotoxic to oral mucosal fibroblasts at concentrations of 4 mmol/L or higher. Exposure of cells to NaF for 2 h also inhibite...

    journal_title:Cell biology and toxicology

    pub_type: 杂志文章

    doi:10.1023/a:1007591426267

    authors: Jeng JH,Hsieh CC,Lan WH,Chang MC,Lin SK,Hahn LJ,Kuo MY

    更新日期:1998-12-01 00:00:00

  • The cytogenetic and hepatotoxic effects of dioxin on mouse liver cells.

    abstract::The cytogenetic and hepatotoxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on mouse liver cells were investigated. Male C57BL/6J strain mice, which have TCDD receptors, were given single intraperitoneal injections of 25, 37.5, 75 and 150 micrograms of TCDD/kg body weight or corn oil carrier alone. Two-third...

    journal_title:Cell biology and toxicology

    pub_type: 杂志文章

    doi:10.1007/BF00141285

    authors: Brooks AL,Jordan SW,Bose KK,Smith J,Allison DC

    更新日期:1988-03-01 00:00:00

  • Effects of fusariotoxin co-exposure on THP-1 human immune cells.

    abstract::Deoxynivalenol (DON), nivalenol (NIV), T-2 toxin (T2), fumonisin B1 (FB1), zearalenone (ZEA), and moniliformin (MON) mycotoxins are common food and feed contaminants produced by Fusarium spp. However, while they are usually found to co-occur in a large range of commodities, only few data are available on mycotoxin co-...

    journal_title:Cell biology and toxicology

    pub_type: 杂志文章

    doi:10.1007/s10565-017-9408-7

    authors: Smith MC,Madec S,Troadec S,Coton E,Hymery N

    更新日期:2018-06-01 00:00:00

  • SEW2871 attenuates ANIT-induced hepatotoxicity by protecting liver barrier function via sphingosine 1-phosphate receptor-1-mediated AMPK signaling pathway.

    abstract::Cholestatic liver injury, a group of diseases characterized with dysregulated bile acid (BA) homeostasis, was partly resulted from BA circulation disorders, which is commonly associated with the damage of hepatocyte barrier function. However, the underlying hepatocyte barrier-protective molecular mechanisms of cholest...

    journal_title:Cell biology and toxicology

    pub_type: 杂志文章

    doi:10.1007/s10565-020-09567-9

    authors: Yang T,Wang X,Zhou Y,Yu Q,Heng C,Yang H,Yuan Z,Miao Y,Chai Y,Wu Z,Sun L,Huang X,Liu B,Jiang Z,Zhang L

    更新日期:2021-01-05 00:00:00

  • Temozolomide induces activation of Wnt/β-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy.

    abstract::Glioblastoma (GBM) is the most aggressive type of glioma. Temozolomide (TMZ) is currently the drug of choice used for post-operative chemotherapy of GBM. However, the presence of intrinsic and acquired resistance hinders the success of chemotherapy. To understand the TMZ resistant mechanisms in glioma, we investigated...

    journal_title:Cell biology and toxicology

    pub_type: 杂志文章

    doi:10.1007/s10565-019-09502-7

    authors: Tomar VS,Patil V,Somasundaram K

    更新日期:2020-06-01 00:00:00

  • Carcinogenicity of chrysotile asbestos: a case control study of textile workers.

    abstract::Chrysotile is the predominant type of asbestos used in the United States and thus represents the most important source of exposure to asbestos already in place. While the steepest exposure-response observed for lung cancer has been in workers exposed to chrysotile in textile operations, some argue that chrysotile is l...

    journal_title:Cell biology and toxicology

    pub_type: 杂志文章

    doi:10.1007/BF00121330

    authors: Dement JM

    更新日期:1991-01-01 00:00:00

  • Histone H4 deacetylation down-regulates catalase gene expression in doxorubicin-resistant AML subline.

    abstract::We explored if epigenetic mechanisms could be involved in the down-regulated expression of catalase gene (CAT) in the doxorubicin-resistant acute myelogenous leukemia (AML)-2/DX100 cells. Down-regulated CAT expression in AML-2/DX100 cells was completely recovered after treatment of hydrogen peroxide (H(2)O(2)) and his...

    journal_title:Cell biology and toxicology

    pub_type: 杂志文章

    doi:10.1007/s10565-011-9201-y

    authors: Lee TB,Moon YS,Choi CH

    更新日期:2012-02-01 00:00:00

  • Galectin 3 acts as an enhancer of survival responses in H. pylori-infected gastric cancer cells.

    abstract::Galectin 3 (Gal-3) is upregulated in gastric epithelial cells as a host response to Helicobacter pylori infection. However, the significance of Gal-3 expression in H. pylori-infected cells is not well established. We analyzed Gal-3 intracellular expression, localization, and its effects in H. pylori-infected gastric e...

    journal_title:Cell biology and toxicology

    pub_type: 杂志文章

    doi:10.1007/s10565-016-9315-3

    authors: Subhash VV,Ho B

    更新日期:2016-02-01 00:00:00

  • Changes in cytosolic CA2+ are not involved in DDT-induced loss of gap junctional communication in WB-F344 cells.

    abstract::Recent studies have demonstrated that the insecticide DDT is a tumor promoting agent. Similar to many other tumor promoting agents, DDT has been shown to inhibit gap junctional intercellular communication (GJIC) between cells in culture, and it has been suggested that DDT-induced loss of communication between adjacent...

    journal_title:Cell biology and toxicology

    pub_type: 杂志文章

    doi:10.1007/BF00249596

    authors: Fransson R,Nicotera P,Wärngård L,Ahlborg UG

    更新日期:1990-04-01 00:00:00

  • Use of cell cultures for predicting the biological effects of mycotoxins.

    abstract::The risk presented by mycotoxins is a toxicological problem. As the data given by physico-chemical analysis may be difficult to translate in terms of toxicity, however, especially when considering multiple contamination, we have developed a system for toxicological analysis of mycotoxins using cell cultures of differe...

    journal_title:Cell biology and toxicology

    pub_type: 杂志文章

    doi:10.1007/BF00122655

    authors: Robbana-Barnat S,Lafarge-Frayssinet C,Frayssinet C

    更新日期:1989-06-01 00:00:00

  • Nitric oxide (NO) donor 3-morpholinosydnonimine antagonizes cyclosporin A-induced contraction in two in vitro glomerular models.

    abstract::Cyclosporin A induces in vivo a severe nephrotoxicity characterized by a large decrease in renal hemodynamics. The aim of this study is to establish the ability of the known NO donor 3-morpholinosydnonimine (SIN-1) to prevent the cyclosporin A-induced contraction by using rat isolated glomeruli and cultured glomerular...

    journal_title:Cell biology and toxicology

    pub_type: 杂志文章

    doi:10.1007/BF00438167

    authors: Potier M,Winicki J,Cambar J

    更新日期:1996-12-01 00:00:00

  • Protective action of fenugreek (Trigonella foenum graecum) seed polyphenols against alcohol-induced protein and lipid damage in rat liver.

    abstract::The study investigates the effect of fenugreek seed polyphenol extract (FPEt) on ethanol-induced damage in rat liver. Chronic ethanol administration (6 g kg(-1) day(-1) x 60 days) caused liver damage that was manifested by excessive formation of thiobarbituric-acid-reactive substances, lipid hydroperoxides, and conjug...

    journal_title:Cell biology and toxicology

    pub_type: 杂志文章

    doi:10.1007/s10565-007-9050-x

    authors: Kaviarasan S,Sundarapandiyan R,Anuradha CV

    更新日期:2008-10-01 00:00:00

  • Degradation of IkappaBalpha in activated RAW264.7 cells is blocked by the phosphatidylinositol 3-kinase inhibitor LY294002.

    abstract::The mechanism by which lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate (PMA) induces production of proinflammatory cytokines in murine macrophages, and the role of phosphatidylinositol 3-kinase (PI3-kinase) have not been well investigated. Activation of nuclear factor kappaB (NF-kappaB) is initiated by the...

    journal_title:Cell biology and toxicology

    pub_type: 杂志文章

    doi:10.1023/a:1015384201785

    authors: Park SJ,Lee SC,Hong SH,Kim HM

    更新日期:2002-01-01 00:00:00

  • Platinum drugs and neurotoxicity: effects on intracellular calcium homeostasis.

    abstract::[Pt(O,O'-acac)(γ-acac)(DMS)] (PtAcacDMS) is a new platinum compound showing low reactivity with nucleobases and specific reactivity with sulfur ligands intracellularly. It induces apoptosis in breast cancer cells, but appears to be less neurotoxic to the developing cerebellum than cisplatin (cisPt). The aim of this st...

    journal_title:Cell biology and toxicology

    pub_type: 杂志文章

    doi:10.1007/s10565-013-9252-3

    authors: Piccolini VM,Bottone MG,Bottiroli G,De Pascali SA,Fanizzi FP,Bernocchi G

    更新日期:2013-10-01 00:00:00

  • Spermine protects alpha-synuclein expressing dopaminergic neurons from manganese-induced degeneration.

    abstract::Manganese exposure is among the many environmental risk factors linked to the progression of neurodegenerative diseases, such as manganese-induced parkinsonism. In animal models, chronic exposure to manganese causes loss of cell viability, neurodegeneration, and functional deficits. Polyamines, such as spermine, have ...

    journal_title:Cell biology and toxicology

    pub_type: 杂志文章

    doi:10.1007/s10565-018-09449-1

    authors: Vijayan B,Raj V,Nandakumar S,Kishore A,Thekkuveettil A

    更新日期:2019-04-01 00:00:00

  • Ability of various inserts to promote endothelium cell culture for the establishment of coculture models.

    abstract::To select an insert suitable for human umbilical vein endothelial cell (HUVEC) culture, we compared several available inserts of 0.2 to 0.45 micron porosity: Cellagen (ICN), Transwell-COL (Costar), Millicell-HA and CM (Millipore), Anopore (Nunc), Cyclopore (Falcon) in comparison with a control surface (Thermanox). The...

    journal_title:Cell biology and toxicology

    pub_type: 杂志文章

    doi:10.1007/BF00438147

    authors: Villars F,Conrad V,Rouais F,Lefebvre F,Amédée J,Bordenave L

    更新日期:1996-12-01 00:00:00

  • alpha-Lipoic acid attenuates x-irradiation-induced oxidative stress in mice.

    abstract::The development of nontoxic but effective radioprotectors is needed because of the increasing risk of human exposure to ionizing radiation. We have reported that alpha-lipoic acid confers considerable radio-protective effect in mouse tissues when given prior to x-irradiation. In the present study, alpha-lipoic acid su...

    journal_title:Cell biology and toxicology

    pub_type: 杂志文章

    doi:10.1007/s10565-006-0137-6

    authors: Manda K,Ueno M,Moritake T,Anzai K

    更新日期:2007-03-01 00:00:00

  • Interaction of benzo[c]phenanthridine and protoberberine alkaloids with animal and yeast cells.

    abstract::We compared the effects of four quaternary benzo[c]phenanthridine alkaloids--chelerythrine, chelilutine, sanguinarine, and sanguilutine--and two quaternary protoberberine alkaloids-berberine and coptisine--on the human cell line HeLa (cervix carcinoma cells) and the yeasts Saccharomyces cerevisiae and Schizosaccharomy...

    journal_title:Cell biology and toxicology

    pub_type: 杂志文章

    doi:10.1023/a:1010907231602

    authors: Slaninová I,Táborská E,Bochoráková H,Slanina J

    更新日期:2001-01-01 00:00:00

  • Genetic toxicity of a mixture of fifteen pesticides commonly found in the Italian diet.

    abstract::To determine the toxicological effects of complex mixtures of pesticides, we obtained data on 100 pesticide residues in common foods of central Italy. Fifteen pesticides were more regularly detected at higher levels (dithiocarbamates, benomyl/carbendazim, thiabendazole, diphenylamine, chlorthalonil, procymidone, fenar...

    journal_title:Cell biology and toxicology

    pub_type: 杂志文章

    doi:10.1007/BF00754461

    authors: Dolara P,Vezzani A,Caderni G,Coppi C,Torricelli F

    更新日期:1993-10-01 00:00:00