Abstract:
:Antimutagenic effects of a novel lipophilic antioxidant, 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ), and other known antioxidants against heterocyclic amine- or other mutagen-induced mutagenesis were examined in the Ames assay using Salmonella strain TA 98 to access the chemo-preventive effects of antioxidants on heterocyclic amine-induced carcinogenesis. Further the mechanisms of inhibition by HTHQ were accessed. HTHQ was shown to potently inhibit mutagenesis induced by all of 8 different heterocyclic amines at rates between 100% and 63% in the presence of S9 mix. When the protection of HTHQ against 2-amino-6- methyldipyrido[1,2-alpha:3',2'-d]imidazole (Glu-P-1)-induced mutagenesis was compared with known antioxidants t-butylhydroquinone, propyl gallate, BHA, BHT and alpha-tocopherol, HTHQ showed the greatest effect. Among hexyl, butyl, ethyl and methyl derivatives of 1-O-alkyl-2,3,5-trimethylhydroquinone, HTHQ was the most effective in inhibiting Glu-P-1-, 3-amino-1-methyl-5-H-pyrido[4,3-b]indole (Trp-P-2)- or 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-induced mutagenesis. On the other hand, HTHQ did not inhibit mutagenic activity induced by other mutagens such as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2) and benzo[a]pyrene. HTHQ weakly inhibited that due to direct mutagen 2-nitro derivative of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) only in the presence of S9 mix. No such influence on a 2-nitro derivative of 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mutagenesis, was observed with or without the S9 mix. HTHQ slightly inhibited mutagenesis induced by activated Glu-P-1, a direct acting proximate metabolite of Glu-P-1, in the absence of the S9 mix. HPLC analysis revealed activated Glu-P-1 to be formed by incubating Glu-P-1 with the S9 mix, but this was considerably decreased by the addition of HTHQ. These results indicate that HTHQ is a powerful antimutagenic compound and specifically acts against heterocyclic amines. Its antimutagenic activity appeared to exert by both inhibiting metabolic activation of heterocyclic amines and action on activated N-hydroxy species.
journal_name
Carcinogenesisjournal_title
Carcinogenesisauthors
Hirose M,Iwata S,Ito E,Nihro Y,Takahashi S,Mizoguchi Y,Miki T,Satoh T,Ito N,Shirai Tdoi
10.1093/carcin/16.9.2227subject
Has Abstractpub_date
1995-09-01 00:00:00pages
2227-32issue
9eissn
0143-3334issn
1460-2180journal_volume
16pub_type
杂志文章相关文献
CARCINOGENESIS文献大全abstract::The influence of the enzymatic inducer beta-naphthoflavone (BNF) and of the inhibitors alpha-naphthoflavone (ANF) and 2-diethylaminoethyl-2,2-diphenylvalerate HCl (SKF 525-A) on the frequency of sister chromatid exchanges (SCE) induced by cyclophosphamide (CPA) was studied in vivo in C57BL/6J male mice. Neither induce...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/4.1.83
更新日期:1983-01-01 00:00:00
abstract::Previous studies have indicated that the Nb rat has a higher predisposition to the spontaneous development of nephroblastoma than most other strains of laboratory rat. In order to determine whether this inherent susceptibility could be exploited as a model for Wilms' tumor, Nb rats were treated with various chemicals ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/6.11.1551
更新日期:1985-11-01 00:00:00
abstract::Telomeres are critical in maintaining chromosome and genomic stability. Arsenic, a human carcinogen as well as an anticancer agent, is known for its clastogenicity. To better understand molecular mechanisms of arsenic actions, we investigated arsenite effects on telomere and telomerase and determined cell growth and a...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgg141
更新日期:2003-11-01 00:00:00
abstract::The JB6 mouse epidermal cell system has been extensively used as an in vitro model for the study of tumor promotion. The present study aimed to assess the relevance of monolayer measurements to the process of transformation, which is induced more efficiently under anchorage-independent (AI) conditions. Although it wou...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/15.5.1001
更新日期:1994-05-01 00:00:00
abstract::3-Methylcholanthrene (3-MC) pretreatment induces the liver microsomal 2-acetylaminofluorene (2-AAF) N-hydroxylase activity of C57BL6 responsive mice. The same pretreatment modifies this enzyme by significantly increasing its apparent Km value which, moreover, becomes protein concentration dependent. After 3-MC inducti...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/3.11.1325
更新日期:1982-01-01 00:00:00
abstract::Conversion of the 2'-deoxyguanosine (dG) residues in calf thymus DNA to 8-hydroxy-2'-deoxyguanosine (8-OH-dG) was achieved at physiological pH by treating the DNA with hydrogen peroxide (H2O2) in the presence of nickel(II) chloride (NiCl2). The effectiveness of this reaction was enhanced by L-histidine (His) which for...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/13.2.283
更新日期:1992-02-01 00:00:00
abstract:BACKGROUND:Variations in genetic mutations in pancreatic carcinoma between different geographical regions have not been studied extensively, especially in developing countries where pancreatic cancer is relatively rare. METHODS:We studied the molecular pathology of 54 pancreatic adenocarcinomas from Egyptian patients ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgm138
更新日期:2007-08-01 00:00:00
abstract::Both Snell dwarf mice (dw/dw) and their phenotypically normal heterozygotes (dw/+) were dosed with methylclofenapate (MCP) at daily intervals by gavage (25 mg/kg). Animals were killed at 12, 24, 36 and 72 h after the initial dose and the parameters of ploidy, nuclearity and DNA synthesis were measured in hepatocytes i...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/11.3.387
更新日期:1990-03-01 00:00:00
abstract::We present data showing that the major phenobarbital inducible cytochromes P-450 (cytochrome P-450IIB1 and cytochrome P-450IIB2) were phosphorylated in intact hepatocytes. This phosphorylation was greatly increased by the cAMP derivatives N6-dibutyryl-cAMP and 8-thiomethyl-cAMP mediated by a cAMP-dependent protein kin...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/10.1.225
更新日期:1989-01-01 00:00:00
abstract::Induction of glutathione S-transferase (GST) enzymes can increase detoxification of carcinogens and reduce carcinogen-induced mutagenesis and tumorigenesis. To determine if the anticarcinogen ellagic acid induces cellular enzymes which detoxify carcinogens, we examined the effect of ellagic acid on the expression of g...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/16.3.665
更新日期:1995-03-01 00:00:00
abstract::Two solid-phase extraction methods were developed for the determination of mutagenic heterocyclic aromatic amines in heated meat products. The copper phthalocyanine (CPC) tandem extraction was performed on coupled cartridges of diatomaceous earth and CPC-derivatized Sephasorb HP, followed by further clean-up on Sephas...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/11.9.1597
更新日期:1990-09-01 00:00:00
abstract::To indicate how readily nitrosamines (NAms) diffuse into the esophagus, we measured diffusion rate (flux) through rat esophagus of dialkyl-NAms using side-by-side diffusion apparatuses. Mucosal and serosal flux at 37 degrees C of two NAms, each at 50 microM, was followed for 90 min by gas chromatography-thermal energy...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/20.5.825
更新日期:1999-05-01 00:00:00
abstract::Overexpressed DNA methyltransferase 1 (DNMT1) strongly contributes to tumor suppressor gene silencing in colorectal cancer (CRC). However, the underlying mechanism of DNMT1 overexpression is still unclear. MicroRNAs (miRNA) have been implicated as gene regulators controlling diverse biological processes, including car...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgr081
更新日期:2011-07-01 00:00:00
abstract::We have previously reported the disposition of benzo[a]pyrene (B[a]P) and its metabolites in male Sprague-Dawley rats following intratracheal instillation of [3H]B[a]P [Weyand, E.H. and Bevan, D.R. (1986) Cancer Res., 46, 5655-5661]. In some experiments, cannulas were implanted in the bile duct of the animals prior to...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/9.11.2027
更新日期:1988-11-01 00:00:00
abstract::Precursor T-cell lymphoblastic neoplasms are aggressive malignancies in need for more effective and specific therapeutic treatments. A significant fraction of these neoplasms harbor deletions on the locus 9p21, targeting the tumor suppressor CDKN2A but also deleting the aconitase 1 (ACO1) gene, a neighboring housekeep...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgz185
更新日期:2020-08-12 00:00:00
abstract::It has recently been reported that the XPD (ERCC2) gene is an integral component of the basal transcription factor TFIIH. We have studied the direct role of this repair gene on the fine structure of DNA repair in hamster cells. The gene and strand specific DNA repair of UV induced pyrimidine dimers was determined in w...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/18.4.681
更新日期:1997-04-01 00:00:00
abstract::The urinary excretion of dimethylnitrosamine (DMN) was studied in male Sprague-Dawley rats. Animals were given DMN (3, 5, 10, 20, 30 and 50 mg/kg body weight, i.p.) or [3H]DMN (0.1, 1 and 3 mg; 8.7, 1.5 and 0.28 mCi/kg body weight, respectively, i.p.) diluted with sterile 0.9% NaCl. Urine was collected for 24 h after ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/2.7.609
更新日期:1981-01-01 00:00:00
abstract::In the present study the role of two families of cytochrome P-450 proteins and the contribution of the cytosolic fraction in the activation of N-nitrosopiperidine to mutagens in the Ames test were investigated. The bioactivation of this nitrosamine was preferentially catalysed by the phenobarbitone-induced cytochromes...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/8.11.1691
更新日期:1987-11-01 00:00:00
abstract::Mevastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol synthesis. Butyrate, a short-chain fatty acid, reduces proliferation and induces differentiation of human colon cancer cells. The aim of our study was to determine the effect of mevastatin, ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/22.7.1061
更新日期:2001-07-01 00:00:00
abstract::The purpose of this study was to examine the activity and associated kinetic parameters of epidermal protein kinase C (PKC) following stimulation by sn-1,2-dioctanoylglycerol (DIC8) or 12-O-tetradecanoylphorbol-13-acetate (TPA) and to examine the relationship between levels of epidermal PKC activity and the induction ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/10.5.833
更新日期:1989-05-01 00:00:00
abstract::Prostate cancer (CaP) is the second leading cause of cancer death in American men. Chronic inflammation has been one of several factors associated with the development of CaP. Single-nucleotide polymorphisms (SNPs) in cytokine genes have been associated with increased inflammation, increased cytokine production and po...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgm277
更新日期:2008-03-01 00:00:00
abstract::It has been proposed that extremely low frequency magnetic fields may enhance tumorigenesis through a co-promotional mechanism. This hypothesis has been further tested using the two-stage model of mouse skin carcinogenesis, i.e. 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced promotion of skin carcinogenesis in mic...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/20.4.685
更新日期:1999-04-01 00:00:00
abstract::Bile acids have been implicated in the aetiology of colon cancer. We have previously found, using 32P-postlabelling, that bile from control patients and from patients with familial adenomatous polyposis (FAP) produces DNA adducts when incubated with salmon sperm DNA in vitro. In the present study we have incubated the...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/15.12.2945
更新日期:1994-12-01 00:00:00
abstract::Liver DNA, obtained at various time intervals from rats chronically fed a choline-devoid diet, was analysed for the presence of aromatic or alkyl adducts by the 32P-postlabeling assay. Alkyl adducts were not detected. Aromatic DNA adduct lesions were revealed, but only at levels (1 adduct per 0.5-3 X 10(9) nucleotides...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/8.1.187
更新日期:1987-01-01 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::Folate and vitamin D have been shown to be influenced by ultraviolet (UV) radiation. UVA radiation can break down plasma folate, whereas vitamin D can be synthesized in UVB-exposed skin. Folate metabolism is involved in DNA synthesis and repair, and vitamin D processes anti-proliferative effects. The functions of both...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgl156
更新日期:2007-02-01 00:00:00
abstract::Azido-IQ (2-azido-3-methylimidazo[4,5-f]quinoline), a novel analog of the food mutagen and carcinogen IQ (2-amino-3-methylimidazo[4,5-f]quinoline) was synthesized and characterized. Both thermolysis and photolysis of this azide yield a short-lived nitrene which can react as an electrophile either directly or via proto...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/9.5.869
更新日期:1988-05-01 00:00:00
abstract::Lung cancer continues to be the leading cause of cancer death in the USA and the best example of a cancer with undisputed evidence of environmental risk. However, a genetic contribution to lung cancer has also been demonstrated by studies of familial aggregation, family-based linkage, candidate gene studies and most r...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgq252
更新日期:2011-03-01 00:00:00
abstract::Sprague-Dawley rats were treated with N-nitrosomorpholine (NNM) alone (7 weeks, 120 mg/l in drinking water), with NNM followed by phenobarbital (PB) (750 mg/l for 6 weeks) or PB alone. The livers from these animals were investigated for glycogen content and activities of glucose-6-phosphatase, glucose-6-phosphate dehy...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/4.7.931
更新日期:1983-01-01 00:00:00
abstract::No previous study has examined the association between mitochondrial DNA copy number (mtCN) and skin cancer risk prospectively. We examined the associations between peripheral blood leukocytes mtCN level and the risks of skin cancers in a case-control study nested within the Nurses' Health Study of non-Hispanic White ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgw072
更新日期:2016-09-01 00:00:00