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 Toxicoljournal_title
Cell biology and toxicologyauthors
Myers JN,Harris KL,Rekhadevi PV,Pratap S,Ramesh Adoi
10.1007/s10565-020-09579-5subject
Has Abstractpub_date
2021-01-07 00:00:00eissn
0742-2091issn
1573-6822pii
10.1007/s10565-020-09579-5pub_type
杂志文章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
更新日期:2008-12-01 00:00:00
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
更新日期:1988-06-01 00:00:00
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
更新日期:1990-04-01 00:00:00
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
更新日期:2017-12-01 00:00:00
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
更新日期:1984-10-01 00:00:00
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
更新日期:1999-01-01 00:00:00
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
更新日期:2008-12-01 00:00:00
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
更新日期:2012-06-01 00:00:00
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
更新日期:1985-10-01 00:00:00
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
更新日期:1995-10-01 00:00:00
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
更新日期:1989-01-01 00:00:00
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
更新日期:1998-12-01 00:00:00
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
更新日期:1988-03-01 00:00:00
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
更新日期:2018-06-01 00:00:00
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
更新日期:2021-01-05 00:00:00
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
更新日期:2020-06-01 00:00:00
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
更新日期:1991-01-01 00:00:00
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
更新日期:2012-02-01 00:00:00
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
更新日期:2016-02-01 00:00:00
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
更新日期:1990-04-01 00:00:00
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
更新日期:1989-06-01 00:00:00
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
更新日期:1996-12-01 00:00:00
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
更新日期:2008-10-01 00:00:00
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
更新日期:2002-01-01 00:00:00
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
更新日期:2013-10-01 00:00:00
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
更新日期:2019-04-01 00:00:00
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
更新日期:1996-12-01 00:00:00
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
更新日期:2007-03-01 00:00:00
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
更新日期:2001-01-01 00:00:00
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
更新日期:1993-10-01 00:00:00