Abstract:
:The aim of this work was to optimize the ionic strength (tau) in the liver microsomal assay (LMA) in performing short-term genotoxicity tests. tau optimization would increase the sensitivity (i.e. decrease false negatives) and at the same time increase the specificity (decrease false positives). Such optimization depends upon the relative activities and stabilities of the liver polysubstrate cytochrome P450- and FAD-containing monooxygenase-dependent metabolizing enzymes present in the incubation mixtures. With regard to phase-I pathway, the expression of various P450-like activities (IA1, IA2, IIB1, IIE1, IIIA P450 classes) and thiobenzamide s-oxidase (as FAD-MFO marker), were examined in terms of their exact incubation conditions for the LMA during a period of preincubation (1 h) over the tau range 0.06-1.40. As a comparison with the phase-II pathway, the behaviour of glutathione S-transferases (total and pi class), glutathione S-epoxide transferase, epoxide hydrolase and UDP-glucuronosyl transferase were studied. Lipid peroxidation (LP) was also determined. Experiments were performed on S9 fractions derived from sodium phenobarbital, beta-naphthoflavone, isosafrol, ethanol and pregnenolone 16-alpha carbonitrile super-induced mouse liver. The maximal value of the mean specific activity (Asp), up to a 46% increase, was found at tau = 0.864 for oxidative reactions considered. On the contrary, a slight modulation of Asp for post-oxidative reactions was seen. LP was not changed appreciably by varying tau. In vitro DNA binding of the well-known premutagenic agent [14C]dimethylnitrosamine ([14C]DMNA), mediated by mouse hepatic microsomal enzymes, showed a significant increase of specific activity at tau = 0.864 (2.25-fold) compared to the usual tau (0.06) used. Additional confirmation of these results stems from mutagenesis experiments using DMNA on the diploid D7 strain of Saccharomyces cerevisiae as a biological test system. Indeed, a significant enhancement of mitotic gene conversion (up to 1.8-fold), mitotic crossing-over (2.6-fold) and reverse point mutation (2.6-fold) frequencies was achieved at tau = 0.86 compared to tau = 0.06 (traditional). These data show that tau = 0.86 can provide more convenient conditions for in vitro bioactivation (as exemplified by an increased Asp phase-I/Asp phase-II ratio), as well as DNA binding and genotoxic response.
journal_name
Carcinogenesisjournal_title
Carcinogenesisauthors
Paolini M,Mesirca R,Pozzetti L,Silingardi P,Grilli S,Cantelli-Forti Gdoi
10.1093/carcin/13.8.1403keywords:
subject
Has Abstractpub_date
1992-08-01 00:00:00pages
1403-8issue
8eissn
0143-3334issn
1460-2180journal_volume
13pub_type
杂志文章相关文献
CARCINOGENESIS文献大全abstract::Despite their individual key roles in promoting head and neck squamous cell carcinoma (HNSCC) progression and treatment resistance, little is known about the impact of intratumoral hypoxia on the activity of the epidermal growth factor receptor (EGFR) signaling pathway in this cancer type. Here, we show that in highly...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgq078
更新日期:2010-07-01 00:00:00
abstract::Maternal nutrition during pregnancy influences the development and metabolism of the fetus. Recent studies suggest that the cancer risk of offspring later in life is associated with maternal diet, but little is known about the effect of a maternal diet high in methyl nutrients on breast cancer risk. Lipotropes are met...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgs125
更新日期:2012-05-01 00:00:00
abstract::Dog urinary bladder is a target organ of carcinogenic arylamines. However, dog hepatic and urothelial cytosols lack acetylation enzymes that are capable of activating N-hydroxy metabolites of arylamines, suggesting that other enzymes may be involved. In the present study, we found that dog liver microsomes were capabl...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/12.10.1887
更新日期:1991-10-01 00:00:00
abstract::Treatment of murine Swiss 3T3 fibroblasts and XB/2 keratinocytes with UV-B light (302 nm) resulted in a dose-dependent inhibition of [125I]epidermal growth factor (EGF) binding. The light dose required to achieve 50% inhibition of binding in both cell types was 80-85 J/m2. Decreased [125I]platelet-derived growth facto...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/11.7.1223
更新日期:1990-07-01 00:00:00
abstract::The regulation of growth hormone 1 (GH1) and insulin-like-growth factor-1 (IGF-1) release is under the influence of three pituitary hormones [growth hormone releasing hormone (GHRH), ghrelin (GHRL) and somatostatin (SST)], which act in an autocrine/paracrine fashion in the breast. By binding to their respective recept...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgl036
更新日期:2006-09-01 00:00:00
abstract::We have examined both the initial nuclease sensitivity and subsequent nucleosome rearrangement of newly repaired regions of chromatin in human diploid fibroblasts treated with methyl methanesulfonate (MMS) and methylnitrosourea (MNU). We initially examined the effect of these two alkylating agents on DNA replicative s...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/5.2.245
更新日期:1984-02-01 00:00:00
abstract::There is some epidemiological support for a protective influence of omega-3 fatty acids against prostate cancer. We wanted to explore whether omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) can affect androgen receptor function in prostate cancer cells. Our study ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/22.8.1201
更新日期:2001-08-01 00:00:00
abstract::In order to test the controversially discussed hypothesis that oval cells are part of a liver stem cell compartment and can give rise to cholangiocellular as well as hepatocellular carcinomas in the course of liver carcinogenesis, we transfected an oval cell line established in our laboratory with an oncogenically act...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/17.12.2635
更新日期:1996-12-01 00:00:00
abstract::Overexpression of the helix-loop-helix protein Id-1 has been reported in over 20 types of cancer. While a number of factors have been demonstrated to regulate Id-1 gene transcription, little is known about the mechanisms responsible for its degradation. In this study, we have demonstrated that Id-1 protein stability w...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgi217
更新日期:2006-02-01 00:00:00
abstract::Chemotherapeutic agents have been the mainstay of cancer therapy for years. However, their effectiveness has been limited by toxicities they impart on normal cells. Staurosporine (ST) has been shown to arrest normal, but not breast cancer, cells in G1. Therefore, ST may become a chemoprotective agent, arresting normal...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgt186
更新日期:2013-10-01 00:00:00
abstract::Previous results in a number of laboratories have demonstrated that epidermal papillomas and carcinomas induced by the two-stage protocol of initiation and promotion contain a point mutation in the 61st codon of the c-Ha-ras oncogene when the initiating agent used is 7,12-dimethylbenz[a]anthracene (DMBA). In the prese...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/9.4.665
更新日期:1988-04-01 00:00:00
abstract::Procarbazine hydrochloride (PCZ), a chemotherapeutic agent used extensively to treat Hodgkins disease and other tumors, induces leukemia, lymphoma, mammary gland and other solid tumors in rodents and non-human primates and is strongly implicated as a leukemogen in humans. Lipotrope (choline and methionine) deficiency ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/11.9.1491
更新日期:1990-09-01 00:00:00
abstract::Manganese superoxide dismutase (Mn-SOD) is strongly expressed in human ovarian cancer, and the serum level of the enzyme is a useful marker for the diagnosis and monitoring of human ovarian cancer. In the present study we found that Mn-SOD was highly expressed in primary and transplanted ovarian cancers in rats induce...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/13.10.1941
更新日期:1992-10-01 00:00:00
abstract::Carcinogen treatment of cultured mammalian cells prior to infection with u.v.-irradiated virus results in enhanced virus survival and mutagenesis suggesting the induction of SOS-type processes. In this paper, we report the development of a primary rat hepatocyte culture system to investigate cellular responses to DNA ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/5.4.495
更新日期:1984-04-01 00:00:00
abstract::Although the anticancer properties of oligomeric proanthocyanidins (OPCs) from grape seeds have been well recognized, the molecular mechanisms by which they exert anticancer effects are poorly understood. In this study, through comprehensive RNA-sequencing-based gene expression profiling in multiple colorectal cancer ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgy034
更新日期:2018-05-28 00:00:00
abstract::The polypeptide hormone epidermal growth factor (EGF) has been shown to enhance adenovirus type 5 transformation of a cloned culture of rat embryo cells (CREF) and X-ray or u.v.-light induced transformation of 10T1/2 mouse embryo cells. In both systems, the degree of enhancement was quantitatively similar to that obse...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/2.3.183
更新日期:1981-01-01 00:00:00
abstract::DNA strand breage in response to damage produced by UV (254 nm) radiation was characterized after permeabilization of diploid normal and xeroderma pigmentosum variant fibroblasts. The breakage reaction required ATP, Mg2+ and sucrose for maximal activity and was inhibited by 150 mM Na+ or K+ and 1 mM N-ethylmaleimide. ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/11.1.15
更新日期:1990-01-01 00:00:00
abstract::The N-hydroxylamine of the carcinogen 2-amino-3-methylimidazolo[4,5-f]quinoline (IQ) covalently bound to calf thymus DNA at pH 7, and the binding was 11% higher under acidic conditions (pH 5). The extent of N-hydroxy-IQ binding to single-stranded polynucleotides at neutral pH was in the following order: polyguanylic a...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/9.6.1061
更新日期:1988-06-01 00:00:00
abstract::3,4-Epoxy-1-butene (EB) is the major mutagenic metabolite of butadiene (BD), an important industrial chemical classified as a probable human carcinogen. Although the mechanism of carcinogenicity of EB is not known, its reactions with nucleophilic sites of DNA giving pro-mutagenic lesions are likely to constitute the e...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/18.1.137
更新日期:1997-01-01 00:00:00
abstract::Serum selenium (Se) levels were measured before, during and after high-dose induction chemotherapy in 70 patients with acute non-lymphocytic leukemia (ANLL). Pre-treatment serum Se levels were lower in patients than in controls (0.082 +/- 0.033 micrograms/ml versus 0.097 +/- 0.035 micrograms/ml, P less than 0.01). Pre...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/10.11.2089
更新日期:1989-11-01 00:00:00
abstract::Human cancers are often associated with numerical and structural chromosomal instability. Structural chromosomal aberrations (CAs) in peripheral blood lymphocytes (PBL) arise as consequences of direct DNA damage or due to replication on a damaged DNA template. In both cases, DNA repair is critical and inter-individual...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgv127
更新日期:2015-11-01 00:00:00
abstract::Nitrosamine-induced hepatocarcinogenesis has been used to investigate the regulation and expression of different drug-metabolizing enzymes in preneoplastic and neoplastic lesions in the female Wistar rat. The enzymes investigated were two phenobarbital-inducible cytochrome P-450 (cyt. P-450) isoenzymes (PB1 and PB2, m...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/6.4.513
更新日期:1985-04-01 00:00:00
abstract::This commentary celebrates the 40th year of Carcinogenesis, spanning 1980-2020 with a focus on lung cancer. For lung cancer, these 40 years come toward the end of a century of scientific inquiry that began with descriptions of this highly fatal malignancy and that closes with emphasis on molecular processes and genomi...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgaa094
更新日期:2020-10-15 00:00:00
abstract::The tissue distribution and macromolecular binding of benzene was studied over a dose range spanning nine-orders of magnitude to determine the nature of the dose-response and to establish benzene's internal dosimetry at doses encompassing human environmental exposures. [14C]-Benzene was administered to B6C3F1 male mic...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/18.12.2421
更新日期:1997-12-01 00:00:00
abstract::As renal cell carcinomas are characterized by the disappearance of the transcription factor LFB1, which is known to be primarily involved in gene regulation in the liver, we have measured the presence of LFB1 in rat hepatocellular carcinomas induced by diethylnitrosamine. The level of LFB1 binding activity in adenoid-...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/16.1.143
更新日期:1995-01-01 00:00:00
abstract::In this study we have investigated the relationship between the dose of 1,2-dimethylhydrazine (DMH) and the yield (and location) of tumours in a mouse strain susceptible to colon tumour induction. Female SWR mice were injected with 6.8 mg/kg DMH i.p. once a week for 1, 5, 10 and 20 weeks and the animals were followed ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/20.3.509
更新日期:1999-03-01 00:00:00
abstract::One hundred forty-seven female Sprague-Dawley rats were divided into 5 groups and at 60 days of age were treated i.g. with 5 mg of 7,12-dimethylbenzanthracene (DMBA) suspended in 1.0 ml of sesame oil. Selenium (Se), as selenium dioxide (SeO2), was administered in the drinking water to 4 of the 5 groups (30 rats/group)...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/2.6.519
更新日期:1981-01-01 00:00:00
abstract::Cancer is a leading cause of death worldwide and environmental factors, including chemicals, have been suggested as major etiological incitements. Cancer statistics indicates that men get more cancer than women. However, differences in the known risk factors including life style or occupational exposure only offer par...
journal_title:Carcinogenesis
pub_type: 杂志文章,meta分析
doi:10.1093/carcin/bgw076
更新日期:2016-10-01 00:00:00
abstract::Four monoclonal antibodies, PhIP-1, -2, -3 and -4, have been produced that bind to PhIP (2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine), a mutagenic aromatic amine produced in meat by cooking. The immunogen was an analog of PhIP conjugated to a carrier protein through the 2-amino group of PhIP, leaving the pyridine...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/10.12.2215
更新日期:1989-12-01 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