Abstract:
:N-Nitrosodimethylamine (NDMA) is a potent mutagen and animal carcinogen to which many people are exposed through the consumption of contaminated food and the use of tobacco products. Although the mutational specificity of NDMA has been studied in bacteria, little is known about the specific types of mutations induced by NDMA in the human genome. Knowledge of the mutational spectrum of NDMA in human genes may help to substantiate the role of NDMA in the etiology of human cancers. In the current study, the mutational spectrum of NDMA was characterized at the tk and hprt loci, in human lymphoblastoid cells capable of metabolically activating NDMA. A number of patterns were observed among NDMA-induced mutations. At both marker loci, G:C-->A:T transitions dominated the mutational spectrum of NDMA, which were indicative of the mutagenicity of the O6meG lesion. In addition, the majority of G:C-->A:T mutations occurred at guanines 3' to another guanine. Almost all of these mutations originated on the non-transcribed strand, which suggests that transcription-coupled repair influenced the distribution of G:C-->A:T transitions at the tk and hprt loci. Furthermore, the observation of hotspots for G:C-->A:T mutations, within both loci, suggests that differential repair kinetics may exist, and consequently affect the distribution of mutations. Finally, a comparison of the site specificity of G:C-->A:T mutations at the tk and hprt loci, indicated that the gene used for mutational analysis influenced the site specificity of NDMA-induced mutations, and possibly reflects the number of 5'-GG-3' sites in the tk and hprt loci that when mutated would yield a mutant phenotype.
journal_name
Carcinogenesisjournal_title
Carcinogenesisauthors
Dobo KL,Eastmond DA,Grosovsky AJdoi
10.1093/carcin/19.5.755subject
Has Abstractpub_date
1998-05-01 00:00:00pages
755-64issue
5eissn
0143-3334issn
1460-2180journal_volume
19pub_type
杂志文章相关文献
CARCINOGENESIS文献大全abstract::The role of tumor estrogen receptors (ERs) and serum estrogen in lung cancer is inconclusive. We investigated the hypothesis that ERs and functional single-nucleotide polymorphisms in the estrogen biosynthesis pathway are associated with poorer lung cancer survival. Lung cancer patients (n = 305) from a National Cance...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgq156
更新日期:2010-10-01 00:00:00
abstract::Treatment of human skin fibroblasts in early S-phase with (+-)7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene (BPDE-I) results in more extensive modification of early replicating DNA than parental DNA. We have investigated the effects of benzamide (BZ) and 3-aminobenzamide (3-ABZ), i...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/13.3.489
更新日期:1992-03-01 00:00:00
abstract::A pilot study was conducted to determine whether any relationship exists between micronucleated cell rates of female uterine cervical epithelium and current smoking status. Cervical uterine cells obtained from 118 pre-menopausal females, seen between September 1994 and June 1995 at the Occupational Medecine Interprofe...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/18.4.749
更新日期:1997-04-01 00:00:00
abstract::An antibody (anti-EH) specific for microsomal epoxide hydrolase (mEH) from rhesus monkey liver has been used to test the immunochemical relationship between human liver mEH and the serum EH levels in human patients with hepatocellular carcinoma (HCC). Immunoblots of separated rhesus monkey and human liver microsomal p...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/10.2.343
更新日期:1989-02-01 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::Diacylglycerols (DAG) are lipid second messengers which are generated during phospholipase-catalyzed hydrolysis of phospholipids. The model DAG, sn-1,2-didecanoylglycerol (DIC10), is an effective topical tumor promoter in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated mouse skin. We now report that 11/12 of DMBA-init...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/14.12.2645
更新日期:1993-12-01 00:00:00
abstract::The effects of retinol and retinoic acid on cytotoxicity and mutation expression at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus in Chinese hamster ovary (CHO) cells with or without exogenous metabolic activation were studied in the presence and absence of known chemical mutagens. Neither retinol ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/9.7.1307
更新日期:1988-07-01 00:00:00
abstract::In hepatocellular carcinoma (HCC), a subset of cells defined by high CD44 and CD133 expression has been reported to possess cancer stem-like cell (CSC) characteristics and to be associated with a poor prognosis. Since the approval of the multi-kinase inhibitor, lenvatinib, for patients with unresectable HCC, two such ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgaa049
更新日期:2020-05-25 00:00:00
abstract::The rates of reaction and the products formed when two vicinal diol-epoxides derived from benz(a)anthracene, anti-BA-3,4-diol 1,2-oxide (t-3,r-4-dihydroxy-t-1,2-oxy-1,2,3,4-tetrahydrobenz(a) anthracene)* and anti-BA-8,9-diol 10,11-oxide (r-8,t-9-dihydroxy-t-10,11-oxy-8,9,10,11-tetrahydrobenz(a)anthracene) reacted with...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/1.3.277
更新日期:1980-03-01 00:00:00
abstract::Male Ah-responsive C57BL/10ScSn mice received a single dose of iron-dextran (600 mg Fe/kg) and were fed a diet containing 0.01% of the PCBs mixture Aroclor 1254 for up to 12 months. Iron caused a marked synergistic increase in liver size from 2 months with greatly elevated mitotic rates, numbers of basophilic foci and...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/11.3.437
更新日期:1990-03-01 00:00:00
abstract::Modification of 3,2'-dimethyl-4-aminobiphenyl (DMAB) multi-organ carcinogenesis by simultaneous treatment with butylated hydroxyanisole (BHA) or butylated hydroxytoluene (BHT) was studied using young and old male F344 rats. Animals, 4 or 54 weeks old, were given DMAB (s.c. injection of 50 mg/kg body wt once a week for...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/12.7.1335
更新日期:1991-07-01 00:00:00
abstract::A plant polysaccharide, Aloe gel extract, was reported to have an inhibitory effect on benzo[a]pyrene (B[a]P)-DNA adduct formation in vitro and in vivo. Hence, chemopreventive effects of plant polysaccharides [Aloe barbadensis Miller (APS), Lentinus edodes (LPS), Ganoderma lucidum (GPS) and Coriolus versicolor (CPS)] ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/20.8.1637
更新日期:1999-08-01 00:00:00
abstract::Prostate cancer (PCa) is the second cause of cancer deaths in men in the USA. When the cancer recurs, early stages can be controlled with hormone ablation therapy to delay the rate of cancer progression but, over time, the cancer overcomes its hormone dependence, becomes highly aggressive and metastasizes. Clinical tr...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgu145
更新日期:2014-10-01 00:00:00
abstract::The NF2 gene encodes the tumor and metastasis suppressor protein Merlin. Merlin exerts its tumor suppressive role by inhibiting proliferation and inducing contact-growth inhibition and apoptosis. In the current investigation, we determined that loss of Merlin in breast cancer tissues is concordant with the loss of the...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgy078
更新日期:2018-09-21 00:00:00
abstract::2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) is a heterocyclic amine mutagen found in cooked meats and is carcinogenic in mice and rats at high doses (mg/kg body wt). Humans, however, are exposed to low amounts (p.p.b.) in the diet, and the effects caused by exposure to human equivalent doses of MeIQx have be...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/16.2.367
更新日期:1995-02-01 00:00:00
abstract::A single i.p. injection of 12-O-tetradecanoylphorbol-13-acetate (TPA) induced a transient increase in the levels of rat liver putrescine, spermidine and spermine. These polyamine concentrations continuously increased until 6 h, immediately following administration of the tumor promoter. Phenobarbital (PB) induced an i...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/5.2.225
更新日期:1984-02-01 00:00:00
abstract::Caucasian renal transplant recipients from Queensland, Australia have the highest non-melanoma skin cancer (NMSC) risk worldwide. Although ultraviolet light (UVR) exposure is critical, genetic factors also appear important. We and others have shown that polymorphism in the glutathione S-transferases (GST) is associate...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgh291
更新日期:2005-01-01 00:00:00
abstract::Male ICR Swiss mice, weighing 16-20 g, were fed ad libitum either a fat-free diet or a diet containing 10% corn oil. After three weeks on these diets, the rates of benzo[a]pyrene (B[a]P) metabolite formation and metabolism to products which covalently bind with macromolecules were compared using hepatic nuclei and mic...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/4.1.9
更新日期:1983-01-01 00:00:00
abstract::MicroRNAs (miRNAs or miR) have been integrated into tumorigenic programs as either oncogenes or tumor suppressor genes. The miR-124 was reported to be attenuated in several tumors, such as glioma, medulloblastoma and hepatocellular carcinoma. However, its role in cancer remains greatly elusive. In this study, we show ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgs383
更新日期:2013-03-01 00:00:00
abstract::The role of rat O6-alkylguanine-DNA alkyltransferase (AGT) in modulating mutagenesis by O6-substituted guanines in the rat H-ras gene was examined. Rat4 cells were transfected with vectors carrying O6-methyl-, O6-ethyl- or O6-benzylguanine residues in place of the normal guanines at either the first, second, or both t...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/14.4.593
更新日期:1993-04-01 00:00:00
abstract::A growing number of studies indicate a link between oxidative stress and cancer. We previously developed a rat model of renal cell carcinoma (RCC) induced by ferric nitrilotriacetate (Fe-NTA). Here, we performed a genome-wide analysis to study characteristics of genomic alteration and identify putative genes involved ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgn255
更新日期:2009-01-01 00:00:00
abstract::In this case-control study with 387 White esophageal patients and 462 White controls matched to cases by age and sex, we evaluated the associations between 13 potential functional polymorphisms in eight major nucleotide excision repair (NER) genes and esophageal cancer risk. In individual single nucleotide polymorphis...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgp058
更新日期:2009-05-01 00:00:00
abstract::4,4'-Methylene-bis(2-chloroaniline) (MOCA) can produce tumors in rodents and dogs and an increased incidence of bladder tumors has been reported in exposed workers. It is therefore of interest to identify the human cytochrome P450 (P450) enzymes involved in MOCA N-oxidation, the primary reaction involved in the format...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/13.2.217
更新日期:1992-02-01 00:00:00
abstract::Caffeine is sequentially metabolized by cytochrome P4501A2 (CYP1A2), N-acetyltransferase (NAT) and/or xanthine oxidase (XO). In the present study the activity of these three enzymes was estimated from ratios of the metabolites formed from dietary caffeine and excreted into the urine collected as spot samples. In the u...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/13.9.1561
更新日期:1992-09-01 00:00:00
abstract::Twist1 is an essential transcription factor required to initiate epithelial-mesenchymal transition (EMT) and promote tumor metastasis. PAQR3 is a newly found tumor suppressor that is frequently downregulated in many types of human cancers. Downregulation of PAQR3 is associated with accelerated metastasis and poor prog...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgw013
更新日期:2016-04-01 00:00:00
abstract::N-Acetoxyarylamines are reactive metabolites that lead to arylamine adduct formation with biological macromolecules. A series of 7-substituted-N-hydroxy-2-acetylaminofluorenes were converted to reactive N-acetoxyarylamines by enzymatic N,O-acyltransfer in the presence of DNA. The N-arylhydroxamic acid substrates that ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/14.8.1651
更新日期:1993-08-01 00:00:00
abstract::3-Amino-1,2,4-triazole, a thyroid carcinogen and goitrogen, is negative in a wide variety of short-term mutagenicity assays. However, amitrole induces gene mutations and morphological transformation in Syrian hamster embryo fibroblasts, cells known to carry out the prostaglandin H synthase (PHS)-mediated peroxidative ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/8.5.659
更新日期:1987-05-01 00:00:00
abstract::Microsatellite instability (MSI) is present in ulcerative colitis (UC) and colitis-associated colorectal cancers (CAC). Certain factors released by polymorphonuclear cells (PMNs) may drive mucosal frameshift mutations resulting in MSI and cancer. Here, we applied a co-culture system with PMNs and colon epithelial cell...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgx118
更新日期:2018-02-09 00:00:00
abstract::Crude plasma membranes were prepared from the liver of control rats or of rats submitted to an initiation by diethyl-nitrosamine and selection with 2-acetylaminofluorene and carbon tetrachloride (group IS) or of rats submitted to an initiation-selection protocol followed by a promotion with phenobarbital (group IS PB)...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/12.4.659
更新日期:1991-04-01 00:00:00
abstract::We have investigated the activity of insoluble and soluble lead compounds in inducing mutagenesis, cell transformation and sister chromatid exchange in mammalian cells. Insoluble lead sulfide, readily phagocytized, was more than four times as toxic to V79 cells on a microM basis, than two moderately soluble lead compo...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/9.10.1727
更新日期:1988-10-01 00:00:00