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 metabolism of other carcinogens. Therefore, we have investigated the peroxidase-mediated binding of [14C]amitrole to macromolecules in vitro. We report here the PHS- and lactoperoxidase-catalyzed binding of [14C]amitrole to protein and tRNA, as well as protein binding by rat and hog thyroid peroxidase. PHS was an order of magnitude more active than lactoperoxidase and two orders of magnitude more active than thyroid peroxidase. The low levels of binding observed with thyroid peroxidase could be explained by the rapid and potent inhibition of this enzyme by amitrole. Although the thyroid peroxidase-mediated binding of amitrole was quite low, it was not inhibitable by compounds that would be expected to be competing substrates in vivo (i.e. I-, monoiodotyrosine, diiodotyrosine). Neither catalase nor horseradish peroxidase catalyzed binding of [14C]amitrole. It was also observed that an interaction between amitrole and protein and/or nucleic acid resulted in the slow generation of hydrogen peroxide, which then served as a substrate to drive peroxidase-mediated binding of [14C]amitrole. These data suggest that PHS may be responsible for conversion of amitrole to a mutagenic intermediate in Syrian hamster embryo cells. Furthermore, the generation of reactive metabolites of amitrole by thyroid peroxidase and/or PHS may contribute to the complete carcinogenicity of this compound by adding a mutagenic response to its potent hormonal effects.
journal_name
Carcinogenesisjournal_title
Carcinogenesisauthors
Krauss RS,Eling TEdoi
10.1093/carcin/8.5.659subject
Has Abstractpub_date
1987-05-01 00:00:00pages
659-64issue
5eissn
0143-3334issn
1460-2180journal_volume
8pub_type
杂志文章相关文献
CARCINOGENESIS文献大全abstract::Most cancer cells show resistance to ionizing radiation (IR)-induced cell death. Recently, Ki-Ras was reported to be responsible for the increased radioresistance. We report here that inhibition of IR-induced activaton of nuclear transcription factor kappa B (NF-kappaB) but not of either Akt or MAPK kinase (MEK), incr...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgi081
更新日期:2005-08-01 00:00:00
abstract::Expression of blood group-related antigens (BGRAs) A, B, H, Le(b), Le(x) and Le(y) was examined immunohistochemically in neoplastic and hyperplastic lesions induced by N-nitrosobis(2-oxopropyl)amine in Syrian hamsters to determine a relationship between histological and biological patterns of the lesion and expression...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/12.3.441
更新日期:1991-03-01 00:00:00
abstract::Formation of O6-ethylguanine (O6EG) in trachea DNA was measured 12 h after acute i.p. administration of 50, 100 and 200 mg diethylnitrosamine (DEN)/kg body wt to Syrian golden hamsters. Purine bases were fractionated by h.p.l.c., and ethylated guanines were quantified optically by fluorescence spectrophotometry. Signi...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/7.9.1457
更新日期:1986-09-01 00:00:00
abstract::Monoterpenes have been shown to both prevent and treat mammary cancer in animal models and are currently in clinical testing in advanced cancer patients. In this study, we investigated a biochemical modulation associated with the antitumor activity of monoterpenes, the inhibition of protein isoprenylation in monoterpe...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/19.5.827
更新日期:1998-05-01 00:00:00
abstract::Rats received a choline-deficient diet containing 0.1% (w/w) DL-ethionine (CDE) for 4, 10, 14 or 22 weeks. A separate group was treated for 4 weeks with CDE and then received a normal diet for 4 weeks. The L and M2 isoenzymes of pyruvate kinase were immunocytochemically demonstrated in liver sections. L-PK expression ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/19.1.99
更新日期:1998-01-01 00:00:00
abstract::Analysis of 24 h urine samples of rats administered N-nitrosodipropylamine (NDPA), N-nitroso-2-hydroxypropylpropylamine (NHPPA) or N-nitroso-2-oxopropylpropylamine (NOPPA) showed that the major excretion product in each case was the beta-glucuronide of NHPPA. This conjugate was shown to be present at levels of about 5...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/2.9.859
更新日期:1981-01-01 00:00:00
abstract::A large series of assays of the hepatocarcinogenic potential of 112 different compounds were carried out using a rapid bioassay system developed in this laboratory based on the two-step concept of hepatocarcinogenesis. Rats were initially given a single dose (200 mg/kg) of diethylnitrosamine (DEN) i.p. and starting 2 ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/9.3.387
更新日期:1988-03-01 00:00:00
abstract::Gastrointestinal tumours are among the most common malignancies in Western society, the majority of which are associated with dietary and lifestyle factors. Many dietary or lifestyle factors have been identified which may have toxic or carcinogenic properties. However, several dietary compounds also able to reduce gas...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgg117
更新日期:2003-10-01 00:00:00
abstract::The effect of transplantation of Yoshida sarcoma cells into rats on the concentrations of both the acute-phase proteins (APPs) in the serum and their mRNAs in the liver has been investigated. In rats that responded to transplantation by forming solid tumors, the serum APP levels increased with tumor size. Some of the ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/12.9.1601
更新日期:1991-09-01 00:00:00
abstract::TP63, a member of the TP53 gene family, encodes two groups of three isoforms (alpha, beta and gamma). The TAp63 isoforms act as transcription factors. The DeltaNp63 isoforms lack the main transcription activation domain and act as dominant-negative inhibitors of transactivation (TA) isoforms. To clarify the role of th...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgm258
更新日期:2008-02-01 00:00:00
abstract::The modifying effects of the phenolic antioxidant catechol (CC) and its analogs hydroquinone (HQ) and resorcinol (RN) on pancreatic carcinogenesis were evaluated in 146 female Syrian golden hamsters. Groups of animals received either saline or 70 mg/kg body wt N-nitrosobis(2-oxopropyl)amine (BOP) s.c. injections, twic...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/12.7.1331
更新日期:1991-07-01 00:00:00
abstract::DNA polymerase beta (polbeta) is a major contributor to mammalian DNA damage repair through its gap-filling DNA synthesis and 5'-deoxyribose phosphate lyase activities. In this way, polbeta plays pivotal roles in the repair of oxidative DNA damage, replication, embryonic survival, neuronal development, meiosis, apopto...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgl239
更新日期:2007-06-01 00:00:00
abstract::The conformation of N-(deoxyguanosin-8-yl)-2-acetylaminofluorene and N-(deoxyguanosin-8-yl)-2-aminofluorene was investigated by 1H n.m.r. spectroscopy. There was rotation about the glycosyl bond and preference for either the anti or syn conformation depended on whether or not the 8-arylamino nitrogen was acetylated. T...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/1.11.955
更新日期:1980-01-01 00:00:00
abstract::Primary cultured newborn mouse epidermal cells cultured in the low Ca2+ (0.02 mM) medium showed typical basal cell morphology and proliferated as a monolayer. A stepwise increase in medium Ca2+ concentration induced terminal differentiation of epidermal cells. In the case of epidermal cells obtained from newborn mice ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/13.8.1301
更新日期:1992-08-01 00:00:00
abstract::The lipoxygenase catalyzed epoxidation of 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP-7,8-diol) was examined. Epoxidation of the BP-7,8-diol was catalyzed by 5- and 15-lipoxygenase in the presence of either arachidonic acid, gamma-linolenic acid, or 15-hydroperoxyeicosatetraenoic acid (15-HPETE). The anti-9,10-epoxy-7...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/10.11.2075
更新日期:1989-11-01 00:00:00
abstract::We have measured the levels of thymine glycol (TG) and thymidine glycol (dTG) in human urine, using an HPLC method. The results show that all 30 specimens examined (including 10 non-neoplastic and 20 neoplastic human urines) contained significant amounts of TG and dTG, average levels (mean +/- SEM) were 0.376 +/- 0.02...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/14.7.1359
更新日期:1993-07-01 00:00:00
abstract::It is now widely accepted that cancer is attributed to the accumulation of genetic alterations in cells. Thus, to understand the molecular mechanisms of cancer metastasis, it is indispensable to identify the genes whose alterations accumulate during cancer progression as well as the genes whose expression is responsib...
journal_title:Carcinogenesis
pub_type: 杂志文章,评审
doi:10.1093/carcin/21.3.497
更新日期:2000-03-01 00:00:00
abstract::Polyphenols have shown promising bioactivity in experimental in vitro and in vivo models for cancer chemoprevention. However, consumed orally, they are often transformed by gut microbes into new active principles with so far incompletely deciphered molecular mechanisms. Here, enterolacton, S-equol and urolithin A as r...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgy158
更新日期:2019-03-12 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::CD133 is a pivotal marker of cancer stem cells (CSCs), which is involved in tumorigenesis and cancer progression. Recent studies have identified CD133 to be a prognostic factor for cancer rested with its expression and genetic variants. Here, we hypothesized that the single nuclear polymorphisms (SNPs) in CD133 may be...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgt181
更新日期:2013-10-01 00:00:00
abstract::The broccoli constituent sulforaphane (1-isothiocyanate-4-methylsulfinylbutane) has previously been shown to protect rats against 9,10-dimethyl-1,2-benz[a]anthracene tumorigenesis, thought to be due, at least in part, to induction of phase II detoxification. We investigated the ability of sulforaphane to also inhibit ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/17.2.277
更新日期:1996-02-01 00:00:00
abstract::The hepatitis B virus X protein (HBx) has pleiotropic biological effects, which underlies its potential role in cell transformation. However, its involvement in hepatic fibrosis remains unclear. In this study, we wanted to clarify, in vivo, the role of HBx protein in the development of liver fibrosis. Mice transgenic ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgz109
更新日期:2020-05-14 00:00:00
abstract::Two new mouse epidermal cell lines have been isolated and characterized as target cells for three chemical carcinogens. The ability to grow these cells at low density (approximately 5 clonogenic cells/cm2) has permitted more precise quantitation of chemical carcinogen-induced changes in epidermal differentiation. The ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/6.9.1245
更新日期:1985-09-01 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::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::Hepatocellular carcinoma (HCC), one of the most prevalent and lethal cancers, has shown an alarming rise in the USA. Without effective therapy for HCC, novel chemopreventive strategies may effectively circumvent the current morbidity and mortality. Oxidative stress predisposes to hepatocarcinogenesis and is the major ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgr045
更新日期:2011-06-01 00:00:00
abstract::The liver-derived human cell line, Hep G2, has high benzo[a]pyrene-metabolizing activity and converts benzo[a]pyrene to intermediates that are mutagenic and that bind to DNA. This cell line will be useful for studying metabolic activation of polycyclic aromatic hydrocarbons and other xenobiotics by human tissue and as...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/1.10.871
更新日期:1980-01-01 00:00:00
abstract::Alterations in the pattern of epidermal cell differentiation and proliferation in mouse skin and benign skin tumors were studied by two-color immunofluorescence using monospecific antibodies. Replicating cells were identified by 5-bromo-deoxyuridine (BrdU) pulse-labeling and differentiating cells by keratins K1 and K1...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/12.11.2063
更新日期:1991-11-01 00:00:00
abstract::We conducted a cross-sectional molecular epidemiological study of coke oven workers exposed to the established carcinogen polycyclic aromatic hydrocarbons (PAHs) to evaluate the relationships between both traditional 'exposure markers' and a series of biomarkers, including urinary 1-hydroxypyrene as a marker of intern...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/19.11.1963
更新日期:1998-11-01 00:00:00
abstract::Understanding the molecular pathways that contribute to the development of tamoxifen resistance is a critical research priority as acquired tamoxifen resistance is the principal cause of poor prognosis and death of patients with originally good prognosis hormone-responsive breast tumors. In this report, we provide evi...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgs105
更新日期:2012-04-01 00:00:00