Abstract:
:Constituents in food and fluids, tobacco chemicals and many drugs are candidates for oral absorption and oxidative metabolism. On this basis, the expression of cytochrome P450 isozymes (CYPs) and the conversion of CYP substrates were analysed in reference to buccal mucosa. A RT-PCR based analysis of human buccal tissue from 13 individuals demonstrated consistent expression of mRNA for the CYPs 1A1, 1A2, 2C, 2E1, 3A4/7 and 3A5. CYP 2D6 was expressed in six out of the 13 specimens, whereas all samples were negative for 2A6 and 2B6. Serum-free monolayer cultures of the Siman virus 40 large T-antigen-immortalized SVpgC2a and the carcinoma SqCC/Y1 buccal keratinocyte lines expressed the same CYPs as tissue except 3A4/7 and 3A5 (SVpgC2a), and 2C, 2D6 and 3A4/7 (SqCC/Y1). Dealkylation of ethoxyresorufin and methoxyresorufin in both normal and transformed cells indicated functional 1A1 and 1A2, respectively. SVpgC2a showed similar activity as normal keratinocytes for both substrates, whereas SqCC/Y1 showed about 2-fold lower 7-ethoxyresorufin O-deethylation and 7-methoxyresorufin O-demethylation activities. SVpgC2a showed detectable and many-fold higher activity than the other cell types towards chlorzoxazone, a substrate for 2E1. Absent or minute catalytic activity of 2C9, 2D6 and 3A4 in the various cell types was indicated by lack of detectable diclofenac, dextromethorphan and testosterone metabolism (<0.2-0.5 pmol/min/mg). Metabolic activation of the tobacco-specific N-nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and the mycotoxin aflatoxin B1 (AFB1) to covalently bound adducts was indicated by autoradiographic analysis of both monolayer and organotypic cultures of SVpgC2a. In contrast, SqCC/Y1 showed lower or absent metabolic activity for these substrates. Finally, measurements of various non-reactive AFB1 metabolites indicated rates of formation <0.1 pmol/min/mg in both normal and transformed cells. The results indicate presence of several CYPs of which some may contribute to significant xenobiotic metabolism in human buccal epithelium. Notably, metabolic activation of AFB1 was not previously implicated for oral mucosa. Further, the results show that CYP-dependent metabolism can be preserved or even activated in immortalized keratinocytes. Metabolic activity in SVpgC2a under both monolayer and organotypic culture conditions suggests that this cell line may be useful to pharmaco-toxicological and carcinogenesis studies.
journal_name
Carcinogenesisjournal_title
Carcinogenesisauthors
Vondracek M,Xi Z,Larsson P,Baker V,Mace K,Pfeifer A,Tjälve H,Donato MT,Gomez-Lechon MJ,Grafström RCdoi
10.1093/carcin/22.3.481keywords:
subject
Has Abstractpub_date
2001-03-01 00:00:00pages
481-8issue
3eissn
0143-3334issn
1460-2180journal_volume
22pub_type
杂志文章相关文献
CARCINOGENESIS文献大全abstract::Several studies have shown that hexavalent chromium [Cr(VI)] induces apoptosis in a variety of in vitro test systems. We instilled intra-tracheally either saline or sodium dichromate (0.25 mg/kg body weight), for three consecutive days, to Sprague-Dawley rats. TUNEL analyses showed a marked increase of the apoptotic i...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/23.4.587
更新日期:2002-04-01 00:00:00
abstract::Medulloblastoma (MB) cells arise from granule neuron precursors (GNPs) that have lost growth control. During normal development, GNPs divide in response to Sonic hedgehog (SHH), a ligand that binds to the patched (PTCH) receptor on GNPs. If one copy of the Ptch gene is lost, as in human Gorlin's syndrome and in Ptch(+...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgt041
更新日期:2013-06-01 00:00:00
abstract::The inability of cells in culture to grow in medium where methionine is replaced by its metabolic precursor, homocysteine, has been linked to neoplastic transformation and termed 'methionine dependence' or 'methionine auxotrophy'. The present investigation was undertaken to establish the influence of intracellular glu...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/12.2.241
更新日期:1991-02-01 00:00:00
abstract::The magnitude of benefit is variable for advanced non-small cell lung cancer (NSCLC) patients receiving platinum-based chemotherapy. The purpose of this study is to determine whether genetic variations in the transforming growth factor-beta (TGF-β) pathway are associated with clinical outcomes in NSCLC patients receiv...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgr067
更新日期:2011-07-01 00:00:00
abstract::Chloroethylnitrosoureas (CNU) are antitumor agents which produce DNA interstrand crosslinks. We have proposed that crosslinks are produced in DNA via monoadduct formation at the guanine-O6 position, followed by a delayed reaction with the opposite DNA strand. Human cells are known to differ in their capacity to repair...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/4.6.759
更新日期:1983-01-01 00:00:00
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
更新日期:1994-06-01 00:00:00
abstract::Recent studies have revealed that 1,2,3,4,6-penta-O-galloyl-beta-d-glucose (PGG) has anti-tumorigenic activity in vitro. In the present work, we evaluated the in vitro and in vivo antiangiogenic and antitumor activities of PGG and examined its molecular mechanisms. PGG significantly inhibited the proliferation and tub...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgi097
更新日期:2005-08-01 00:00:00
abstract::Previous studies have shown that polycyclic aromatic hydrocarbons (PAHs) mobilize intracellular Ca2+ in human T cells by inositol trisphosphate-dependent mechanisms resulting from activation of phospholipase C-gamma by SRC-related protein tyrosine kinases, thereby mimicking antigen-receptor activation. Ca2+ appears to...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/18.6.1177
更新日期:1997-06-01 00:00:00
abstract::Recent evidence demonstrates the existence of diversified microbiota in the lung. However, the effect of lung carcinogenesis on the flora in lung microenvironment has yet not been well investigated. In this study, we surveyed the microbial composition and diversity in lung tumor and paired adjacent normal tissues obta...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgaa044
更新日期:2020-08-12 00:00:00
abstract::Inbred strains of mice with differential response to known tumor promoters were compared with respect to their susceptibility to modulation of hepatic antioxidant enzymes by long-term treatment with high fat diet (HF) and phenobarbital (PB). Mice of the C57BL/6J (C57), C3H/HeOuJ (C3H) and DBA/2J (DBA) strains were fed...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/14.6.1225
更新日期:1993-06-01 00:00:00
abstract::Previous research suggests that far upstream element-binding protein 1 (FUBP1) plays an important role in various tumors including epatocellular carcinoma (HCC). However, the role of FUBP1 in liver cancer remains controversial, and the regulatory pathway by FUBP1 awaits to be determined. This study aims to identify th...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgz171
更新日期:2020-07-14 00:00:00
abstract::Copenhagen (Cop) rats are completely resistant to the chemical induction of mammary adenocarcinomas, but their susceptibility to hepatocarcinogenesis is virtually unknown. Rat liver is a well-characterized and easily manipulated tissue in which to study carcinogenesis. Therefore, if Cop rats are resistant to hepatocar...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/18.9.1745
更新日期:1997-09-01 00:00:00
abstract::A new sensitive 32P-postlabeling assay for DNA adducts has been developed in which DNA is hydrolyzed initially by nuclease P1 and prostatic acid phosphatase instead of micrococcal nuclease and spleen phosphodiesterase as employed in previous postlabeling procedures. When DNA containing bulky adducts, X1, X2, .....Xn, ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/10.7.1231
更新日期:1989-07-01 00:00:00
abstract::Docosahexaenoic acid (DHA), a 22:6 n-3 polyunsaturated fatty acid, is the longest and most highly unsaturated fatty acid found in most membranes and has been shown to inhibit cancer cell growth in part by modifying cell signaling. In the current study, alterations to epidermal growth factor receptor (EGFR) signaling u...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgq111
更新日期:2010-09-01 00:00:00
abstract::Disulfiram (DSF) can considerably alter the organotropy of chemical carcinogens. For N-nitrosodimethylamine and for N-nitrosodiethylamine the organotropy is shifted from the liver to the nasal cavity or the oesophagus, respectively. Whereas the influence of DSF or its metabolites on enzyme systems has been studied, li...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/3.5.563
更新日期:1982-01-01 00:00:00
abstract::The survival of transfected simian virus (SV) 40 DNA is acutely sensitive to damage in a 302-bp regulatory region that governs viral gene expression and the initiation of viral DNA replication. We investigated whether the lethal effect of damage in this region is due to the disruption of gene expression or to the inhi...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/8.8.1133
更新日期:1987-08-01 00:00:00
abstract::The G protein-coupled formylpeptide receptor (FPR), known to mediate phagocytic leucocyte chemotaxis in response to bacterial- and host-derived agonists, was expressed by tumor cells in specimens of surgically removed more highly malignant human gliomas. In human glioblastoma cell lines, FPR activation increased cell ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgn266
更新日期:2009-02-01 00:00:00
abstract::Alcohol is a major risk factor for oesophageal squamous cell carcinoma (OSCC), the most prevalent histological subtype of oesophageal cancer (OC) worldwide. The metabolism of alcohol is regulated by specific enzymes whose activity and expression is influenced by genetic polymorphisms. We conducted a systematic review ...
journal_title:Carcinogenesis
pub_type: 杂志文章,评审
doi:10.1093/carcin/bgx067
更新日期:2017-09-01 00:00:00
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
更新日期:2018-10-08 00:00:00
abstract::High intake of red meat is associated with an increased risk of colon cancer. It has been suggested that fat from red meat is responsible, because high fat intake increases the concentration of cytotoxic lipids in the colon. Experimental studies have not unequivocally supported such a role for fat, however. Recently, ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/21.10.1909
更新日期:2000-10-01 00:00:00
abstract::Recent studies have examined and demonstrated the potential cancer chemopreventive activity of freeze-dried berries including strawberries and black raspberries. Although ellagic acid, an abundant component in these berries, has been shown to inhibit carcinogenesis both in vivo and in vitro, several studies have repor...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/22.2.351
更新日期:2001-02-01 00:00:00
abstract::The karyopherin β proteins are involved in nuclear-cytoplasmic trafficking and are crucial for protein and RNA subcellular localization. We previously showed that Kpnβ1, a nuclear importin protein, is overexpressed in cervical cancer and is critical for cervical cancer cell survival and proliferation, whereas non-canc...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgt491
更新日期:2014-05-01 00:00:00
abstract::Adduct formation has been considered to be a major causal factor of DNA damage by carcinogenic heterocyclic amines. By means of experiments with an electrochemical detector coupled to a high-performance liquid chromatograph, we revealed that N-hydroxy metabolite of 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (Ph...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/23.5.855
更新日期:2002-05-01 00:00:00
abstract::Cancer of the stomach is one of the most commonly diagnosed malignancies and remains an important cause of mortality world wide. This type of cancer is not uniformly distributed among populations but shows a marked variation in both incidence and mortality. Although gastric cancer is declining in many parts of the wor...
journal_title:Carcinogenesis
pub_type: 杂志文章,评审
doi:10.1093/carcin/20.12.2195
更新日期:1999-12-01 00:00:00
abstract::The antitumorigenic activities of polyphenols such as ellagitannins and anthocyanins in pomegranate (Punica granatum L.) have been previously studied where cytotoxic, anti-inflammatory and antioxidant effects were evident in various cancer models. The objective of this study was to investigate the role of miR-126/vasc...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgt295
更新日期:2013-12-01 00:00:00
abstract::Several converging lines of evidence suggest that keratinocyte stem cells including those clonogenic in vitro, are the target cells in skin carcinogenesis. However, the mechanism of their involvement in carcinogenesis continues to be unknown. Recently, we have demonstrated that the number of keratinocyte clonogenic st...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/24.3.417
更新日期:2003-03-01 00:00:00
abstract::O6-Alkylguanine-DNA alkyltransferase (AGAT) activity was determined in macroscopically normal peripheral lung tissues from 122 patients undergoing lung surgery. AGAT activity of smokers was 1.4-fold higher than that of lifetime non-smokers (P = 0.030). Less than one year of abstinence from smoking did not cause a sign...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/15.8.1535
更新日期:1994-08-01 00:00:00
abstract::The activity of nuclear transcription factors is often regulated by specific kinase-signaling pathways. We have previously shown that the organochlorine pesticide dichlorodiphenyltrichloroethane (DDT) stimulates activator protein-1 activity through the p38 mitogen-activated protein kinase (MAPK). Here, we show that DD...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgn213
更新日期:2009-01-01 00:00:00
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
更新日期:1989-11-01 00:00:00
abstract::Heat treatment of foods containing reducing sugars and amino acids during cooking or sterilization triggers a sequence of non-enzymatic reactions collectively known as the Maillard reaction. 5-Hydroxymethylfurfural (HMF), one of the major intermediate products in the Maillard reaction, has been found to possess cytoto...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/15.10.2375
更新日期:1994-10-01 00:00:00