Abstract:
:Metabolism and macromolecular interaction of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were studied in human buccal mucosa in vitro. Microautoradiographic analysis of [5-3H]NNK-exposed explant cultures demonstrated a uniform distribution of bound radioactivity in the mucosal epithelium, without significant binding in the underlying connective tissue. The metabolism of [5-3H]NNK at concentrations of both 6 and 100 microM resulted in seven identified metabolites in both explant and epithelial cell cultures. Formation of 4-(methylnitrosamino)-1-(3-pyridyl)butan-1-ol by carbonyl reduction of NNK accounted for almost 95% of the total metabolism, whereas the proportions of other metabolites obtained by alpha-carbon hydroxylation and pyridine N-oxidation reactions varied from undetectable levels to approximately 2% in both experimental systems. A positive correlation between concentration and the metabolic route associated with the formation of DNA methylating intermediates (alpha-hydroxylation at the N-methylene carbon) was found, i.e. when the concentration of NNK was raised from 6 to 100 microM, keto-acid formation which in part reflects DNA methylation was increased preferentially over ketoalcohol production, an index of DNA pyridyloxobutylation. Both the total rate of NNK metabolism and the amount of protein adducts were higher in cells from primary cultures up to the third passage than in explants cultured for 1 day. Between 10(-9) to 10(-4) M, neither NNK nor its precursor alkaloid nicotine affected the colony forming efficiency of normal and tumorous buccal epithelial cells, although at 10(-3) M each agent inhibited this function. Taken together, the results demonstrate the capability of human buccal mucosal epithelium to metabolize NNK by three major pathways, including those involved in the formation of adducts with cellular macromolecules.
journal_name
Carcinogenesisjournal_title
Carcinogenesisauthors
Liu Y,Sundqvist K,Belinsky SA,Castonguay A,Tjälve H,Grafström RCdoi
10.1093/carcin/14.11.2383subject
Has Abstractpub_date
1993-11-01 00:00:00pages
2383-8issue
11eissn
0143-3334issn
1460-2180journal_volume
14pub_type
杂志文章相关文献
CARCINOGENESIS文献大全abstract::Catechol (1,2-dihydroxybenzene) is a major phenolic compound present in the co-carcinogenic fraction of cigarette tar. It has been shown to be a potent co-carcinogen with benzo[a]pyrene (BaP) in mouse skin. In this study we have examined the co-carcinogenic and co-initiating activities of catechol with racemic and ena...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/10.10.1897
更新日期:1989-10-01 00:00:00
abstract::The dorsal skins of 6-8 week old female SENCAR mice were initiated with a single application of 10 nmol of 7,12-dimethylbenz[a]anthracene (DMBA) and subsequently promoted twice/week with topical applications of vitamin E (dl-alpha-tocopherol, 80 mumol/treatment). Vitamin E from two separate commercial suppliers was te...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/14.4.659
更新日期:1993-04-01 00:00:00
abstract::Heterocyclic aromatic amines (HAAs), formed during the cooking of foods, are known to induce tumours in rodent bioassays and may thus contribute to human cancer risk. We tested six HAAs in a morphological transformation assay and in three in vitro genotoxicity assays. The morphological transforming abilities of HAAs w...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/20.4.545
更新日期:1999-04-01 00:00:00
abstract::The underlying molecular mechanisms of the tumor-promoting activity of bile acids such as chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA) and the protective effect of ursodeoxycholic acid (UDCA) remain largely unclear. Using RNA arbitrarily primed PCR (RAP-PCR) for differential display, we identified, cloned a...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/19.11.1901
更新日期:1998-11-01 00:00:00
abstract::The effect of glucose on the formation of the food mutagen PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) was studied in a model system. When a mixture of creatine (0.9 mmol), phenylalanine (0.9 mmol) and glucose (0.45 mmol) was heated in diethylene glycol and water (3 ml, 5:1) for 10 min at 180 or 225 degrees...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/12.12.2297
更新日期:1991-12-01 00:00:00
abstract::Inflammatory tumor microenvironments play pivotal roles in the development of cancer. Inflammatory cytokines such as CXCL1/GROα exert cancer-promoting activities by increasing tumor angiogenesis. However, whether CXCL1/GROα also plays a role in the progression of prostate cancer, particularly in highly invasive castra...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgs299
更新日期:2012-12-01 00:00:00
abstract::The nitrogen heterocycle dibenz[c,h]acridine (DB[c,h]ACR) and the enantiomers of the diastereomeric pair of bay-region 3,4-diol 1, 2-epoxides as well as other bay-region epoxides and dihydrodiol derivatives of this hydrocarbon have been evaluated for tumorigenicity on mouse skin and in the newborn mouse. On mouse skin...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/21.11.1997
更新日期:2000-11-01 00:00:00
abstract::Structural analogs of diethylstilbestrol (DES) with at least one phenolic hydroxyl group are metabolized by prostaglandin H synthase (PHS) from ram seminal vesicle microsomes (RSVM) in vitro in the presence of arachidonic acid (20:4). U.v. spectroscopy revealed the formation of p-quinoid intermediates in incubations o...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/7.1.137
更新日期:1986-01-01 00:00:00
abstract::The LEC rat spontaneously develops liver cancer after suffering chronic liver injury caused by abnormal copper accumulation in the liver, but the role of copper accumulation in the induction of liver cancer remains obscure. We histochemically and biochemically examined the content of copper and metallothionein (MT), a...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/15.9.1833
更新日期:1994-09-01 00:00:00
abstract::Lung cancer is the leading cause of cancer-related death, with non-small cell lung cancer (NSCLC) being the predominant form of the disease. Most lung cancer is caused by the accumulation of genomic alterations due to tobacco exposure. To uncover its mutational landscape, we performed whole-exome sequencing in 31 NSCL...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgs148
更新日期:2012-07-01 00:00:00
abstract::Apolipoprotein E (apoE) plays a major role in the metabolism of bile acids, cholesterol and triglycerides, and has recently been proposed as being involved in the carcinogenic process. Given the potential role of bile acids in colorectal cancer etiology, it is reasonable that colorectal cancer risk might be modified b...
journal_title:Carcinogenesis
pub_type: 杂志文章,多中心研究
doi:10.1093/carcin/bgi088
更新日期:2005-08-01 00:00:00
abstract::Cisplatin alone or in combination with 5FU (5-fluorouracil) and docetaxel (TPF) are common regimen chemotherapeutics for treatment of advanced oral squamous cell carcinoma (OSCC). Despite the initial positive response, several patients experience relapse due to chemoresistance. The potential role of Bcl-2 antiapoptoti...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgy135
更新日期:2019-03-12 00:00:00
abstract::The experiments reported in this study were designed to examine the question of whether a mammary epithelial cell's independence from hormonal requirements is established at the time of carcinogenic initiation, or whether the emergence of hormone independence is associated with the process of tumor progression. A newl...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/19.3.383
更新日期:1998-03-01 00:00:00
abstract::Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide. Despite progress in developing chemotherapeutics for the treatment of NSCLC, primary and secondary resistance limits therapeutic success. NSCLC cells exhibit multiple mutations in the epidermal growth factor receptor (EGFR), which c...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgt365
更新日期:2014-03-01 00:00:00
abstract::Cyclic 1,N2-propanodeoxyguanosine adducts are formed in vitro in DNA treated with alpha-acetoxy-N-nitrosopyrrolidine or its metabolite, crotonaldehyde. However, the in vivo formation of these cyclic adducts in DNA has not been demonstrated due to the lack of a sensitive detection method. In this study, a 32P-postlabel...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/10.7.1291
更新日期:1989-07-01 00:00:00
abstract::We report evidence that the mutagen and carcinogen 3-amino-1-methyl-5H pyrido[4,3b]indole (Trp P-2) is a substrate for co-oxidation by prostaglandin H synthase (PHS) in ram seminal vesicle (RSV) microsomes. Trp P-2 serves as a reducing cofactor for the hydroperoxidase activity of PHS as shown by the concentration-depe...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/7.8.1397
更新日期:1986-08-01 00:00:00
abstract::Here we report that colorectal cancer patients show a markedly higher frequency (3-fold) of wild-type NAT2*4 allele homozygotes than the control population. However, a marked difference in NAT2*4/NAT2*4 genotype frequency associated with the patients gender was observed pointing to a male-specific effect of this genot...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/19.1.37
更新日期:1998-01-01 00:00:00
abstract::Telomerase activity in cancer cells is dependent on the transcriptional regulation of the human telomerase reverse transcriptase (hTERT) gene, encoding the catalytic subunit of human telomerase. We have shown previously that HTLV-1 basic leucine zipper (HBZ), a viral regulatory protein encoded by the human retrovirus,...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgt221
更新日期:2013-11-01 00:00:00
abstract::Pancreatic cancer has remained refractory to treatment. In large part, this results from the lack of an animal model that mimics pancreatic cancer in man. We describe a novel experimental model of pancreatic cancer that shares the genetic background, histologic features and natural history of human mixed acinar-ductal...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgx119
更新日期:2018-02-09 00:00:00
abstract::The effect of changing the format of administration as well as the total dose of the promoting agent phenobarbital (PB) on the development of altered hepatic foci (AHF) was determined in an initiation-promotion protocol with female rats fed the purified AIN-76 diet. Effects on the total number of AHF and the volume pe...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/12.6.1009
更新日期:1991-06-01 00:00:00
abstract::Previous metabolism and DNA-binding studies indicated that 5,6-dimethylchrysene (5,6-diMeC) is metabolically activated in mouse skin through formation of its 1,2-dihydrodiol (5,6-diMeC-1,2-diol) and bay region diol-epoxide (anti-5,6-diMeC-1,2-diol-3,4-epoxide). These metabolites were tested as tumor initiators on mous...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/14.10.2033
更新日期:1993-10-01 00:00:00
abstract::Insulin-like growth factor 1 receptor (IGF-1R) activation is required for prostate cell proliferation. Prostate cancer is one of the most commonly diagnosed malignant tumors in Western countries. Overexpression of IGF-1R in prostate cancer is associated with tumor growth. These suggest that IGF-1R inhibitory agents ma...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgl189
更新日期:2007-03-01 00:00:00
abstract::The present study was designed to compare the skin tumor promoting and epidermal ornithine decarboxylase (ODC) inducing activities of various structural analogs of anthralin (1,8-dihydroxy-9-anthrone) and chrysarobin (1,8-dihydroxy-3-methyl-9-anthrone). Groups of 30 SENCAR mice each were initiated with 7,12-dimethylbe...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/9.8.1437
更新日期:1988-08-01 00:00:00
abstract::Male and female strain A/J mice were exposed to a mixture of cigarette sidestream and mainstream smoke at a chamber concentration of total suspended particulates of 82.5 mg/m3. Exposure time was 6 h/day, 5 days/week for 5 months. The animals were allowed to recover for another 4 months in filtered air before sacrifice...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/19.10.1789
更新日期:1998-10-01 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::We previously characterized a clone of CHO cells, clone B, that displayed tolerance to the cytotoxic effects of N-methylnitrosourea (MNU) and 6-thioguanine (6-TG). To determine whether this phenotype affected the mutagenic response of the cells, MNU-induced mutation to 8-azaadenine resistance (8-AAr) was measured in t...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/14.10.2097
更新日期:1993-10-01 00:00:00
abstract::Whole-body autoradiography of [3H]aflatoxin B1 ([3H]AFB1) in lamb showed a localization of bound labelling, in addition to the liver, in the nasal olfactory and respiratory mucosa, in the mucosa of the nasopharynx, pharynx, oesophagus, larynx, trachea, bronchi and bronchioles and in the palpebral and bulbar conjunctiv...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/15.5.947
更新日期:1994-05-01 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::A decreased incidence of squamous cell carcinoma of the head and neck (SCCHN) associated with fruit and vegetable intake may act through chemopreventive compounds, which may be more available to persons homozygous for the deletion genotypes of the glutathione S-transferase (GST). We evaluated interactions between frui...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgh054
更新日期:2004-05-01 00:00:00
abstract::Patients with inflammatory bowel diseases are at increased risk for colorectal cancer. Pharmacological inhibition of cyclooxygenase (COX) function exacerbates symptoms in colitis patients. Animal models of colitis using Cox-2-knockout mice and COX inhibitors also indicate that COX-2 has a protective role against colon...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgq268
更新日期:2011-03-01 00:00:00