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151.
Heikkinen P Ernst H Huuskonen H Komulainen H Kumlin T Mäki-Paakkanen J Puranen L Juutilainen J 《Radiation research》2006,166(2):397-408
This study evaluated possible effects of radiofrequency (RF) radiation on tumorigenesis induced by the mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) given in drinking water. Female Wistar rats aged 7 weeks at the beginning of the experiments were randomly divided into four groups of 72 animals: a cage-control group and three MX-exposed groups (a daily average dose of 1.7 mg MX/kg body weight for 104 weeks), of which two were exposed to 900 MHz pulsed RF radiation and the third served as a sham-RF-radiation group. The RF-radiation groups were exposed 2 h per day, 5 days per week for 104 weeks at nominal whole-body average SARs of 0.3 W/kg and 0.9 W/kg. Complete histopathology was performed on the rats of the three MX-exposed groups. The tumor types and incidences observed in the MX-exposed animals were similar to those reported earlier in MX-exposed female Wistar rats. RF radiation did not statistically significantly affect mortality or organ-specific incidence of any tumor type. The only statistically significant difference was an increase in the combined frequency of vascular tumors of the mesenteric lymph nodes in the high-RF-radiation group compared to the sham-RF-radiation group. However, additional histopathological analysis of the cage-control animals suggested that this difference was due to unusually low frequency of this type of tumor in the sham-RF-radiation group rather than a high frequency in the high-RF-radiation group. With respect to non-neoplastic findings, statistically significant differences between the RF-radiation groups and the sham-RF-radiation group were observed only for single findings in the lacrimal glands, lungs, liver and skin. Such changes are commonly seen in aged rats and were considered to be unrelated to RF radiation. The results of the present study do not support co-carcinogenic effects of low-level long-term RF-radiation exposure in rats. 相似文献
152.
Susanna M. Nieminen Jorma Mki-Paakkanen Maija-Riitta Hirvonen Marjut Roponen Atte von Wright 《Mutation Research - Genetic Toxicology and Environmental Mutagenesis》2002,520(1-2):161-170
The genotoxic effects of gliotoxin, a known fungal secondary metabolite, were studied. Gliotoxin was purified from cultivation medium of Aspergillus fumigatus isolated from the indoor air of a moisture problem house. The genotoxicity of gliotoxin was assessed both in bacterial test systems including bacterial repair assay, Ames Salmonella assay and SOS-chromotest, and in mammalian cells using single cell gel (SCG) electrophoresis assay and sister-chromatid exchange (SCE) test. Gliotoxin was found to be genotoxic in the bacterial repair assay but, not in the Salmonella test or SOS-chromotest. A dose-related increase in DNA damage was observed in mouse RAW264.7 macrophages exposed to gliotoxin for 2 h in plain medium in the SCG assay. In contrast to the positive response in the SCG assay, gliotoxin did not induce any clear, dose-related increase in SCEs in Chinese hamster ovary (CHO) cells. 相似文献
153.
154.
Arsi Ikonen Mika Sipura Sari Miettinen & Jorma Tahvanainen 《Entomologia Experimentalis et Applicata》2003,108(3):179-185
We examined preference and performance of four Finnish Galerucella lineola F. populations on alder and willow. In standardized two‐choice laboratory feeding trials with alder and willow, only two naturally alder‐associated G. lineola populations accepted alder. Two conspecific willow‐associated populations preferred willow. These preferences seem to be unstable, however, because they can be modified by the beetles’ experience. Thus, there probably is not a complete host preference‐based isolation of alder‐ and willow‐associated G. lineola beetles in nature. In performance experiments, larvae of all four populations survived better on willow than on alder. This may indicate that willows are the ancestral hosts for G. lineola. Nevertheless, larvae of the two alder‐associated G. lineola populations survived better on alder than larvae of the two willow‐associated populations. On the other hand, larvae of the two willow‐associated populations survived better on willow than larvae of the two alder‐associated populations. This performance trade‐off suggests that G. lineola encounters different selective pressures on alders and willows. On both of them, selection probably disfavours those G. lineola genotypes that are the most successful and abundant on alternative hosts. This may reduce the effects of gene flow that is likely to occur as a consequence of incomplete host preference‐based isolation of alder‐ and willow‐associated G. lineola populations. Data from pupal weights support the idea that alder‐ and willow‐associated G. lineola populations may be genetically differentiated. Pupae of the two alder‐associated populations were heavier than those of the willow‐associated populations irrespective of whether larvae had fed on alder or on willow. Overall, our results indicate host race formation in G. lineola. This process may be enforced by the variable abundance of alders and willows in local communities. 相似文献
155.
Autoreactive CD4(+) T cells contribute to the destruction of insulin producing beta cells in Type 1 diabetes (T1D). Using MHC class II tetramers, we have analyzed the frequency of GAD65- (274-286; 555-567) and insulin- (A1-15; A6-21) specific CD4(+) T cells in 31 children with T1D, 65 multiple autoantibody-positive children and 93 HLA- and age-matched controls. In a smaller group of children T-cell responses of memory origin to the same autoantigens were investigated. We observed a higher response to GAD65 555-567 in the autoantibody-positive children than in the controls (P=0.017). Memory T-cell responses to GAD65 555-567 were more frequent among T1D patients (P=0.025) and autoantibody-positive (P=0.054), while all controls were negative (n=28). In summary, the presence of antigen experienced GAD65-specific T cells in the subjects with diabetes-associated autoimmunity is encouraging for further directions in the prediction of T1D. 相似文献
156.
Androgen receptor acetylation governs trans activation and MEKK1-induced apoptosis without affecting in vitro sumoylation and trans-repression function 下载免费PDF全文
Fu M Wang C Wang J Zhang X Sakamaki T Yeung YG Chang C Hopp T Fuqua SA Jaffray E Hay RT Palvimo JJ Jänne OA Pestell RG 《Molecular and cellular biology》2002,22(10):3373-3388
The androgen receptor (AR) is a nuclear hormone receptor superfamily member that conveys both trans repression and ligand-dependent trans-activation function. Activation of the AR by dihydrotestosterone (DHT) regulates diverse physiological functions including secondary sexual differentiation in the male and the induction of apoptosis by the JNK kinase, MEKK1. The AR is posttranslationally modified on lysine residues by acetylation and sumoylation. The histone acetylases p300 and P/CAF directly acetylate the AR in vitro at a conserved KLKK motif. To determine the functional properties governed by AR acetylation, point mutations of the KLKK motif that abrogated acetylation were engineered and examined in vitro and in vivo. The AR acetylation site point mutants showed wild-type trans repression of NF-kappa B, AP-1, and Sp1 activity; wild-type sumoylation in vitro; wild-type ligand binding; and ligand-induced conformational changes. However, acetylation-deficient AR mutants were selectively defective in DHT-induced trans activation of androgen-responsive reporter genes and coactivation by SRC1, Ubc9, TIP60, and p300. The AR acetylation site mutant showed 10-fold increased binding of the N-CoR corepressor compared with the AR wild type in the presence of ligand. Furthermore, histone deacetylase 1 (HDAC1) bound the AR both in vivo and in cultured cells and HDAC1 binding to the AR was disengaged in a DHT-dependent manner. MEKK1 induced AR-dependent apoptosis in prostate cancer cells. The AR acetylation mutant was defective in MEKK1-induced apoptosis, suggesting that the conserved AR acetylation site contributes to a pathway governing prostate cancer cellular survival. As AR lysine residue mutations that abrogate acetylation correlate with enhanced binding of the N-CoR repressor in cultured cells, the conserved AR motif may directly or indirectly regulate ligand-dependent corepressor disengagement and, thereby, ligand-dependent trans activation. 相似文献
157.
Esa Tahvanainen Henrik Forsius Margareta Damsten Elvi Karila Juha Kolehmainen Jean Weissenbach Pertti Sistonen Albert de la Chapelle 《Genomics》1995,30(3)
We recently assigned a gene for autosomal recessive cornea plana congenita (CNA2; MIM No. 217300) by linkage analysis to the approximately 3-cM interval between markers D12S82 and D12S327. Here, we extended these studies by exploiting the haplotype and linkage disequilibrium information that can be derived from the genetically isolated Finnish population and its subpopulations. By testing 32 independent families with 10 polymorphic markers in the CNA2 interval, strong allelic association between CNA2 and a set of markers with a peak at marker D12S351 was detected. Based on linkage disequilibrium analysis, the critical region for CNA2 could be narrowed to only 0.04-0.3 cM from marker D12S351, thus defining a critical interval 0.08-0.60 cM in length. These results provide a basis for highly focused positional cloning of CNA2. 相似文献
158.
Jorma Keski-Oja Kari Alitalo Aarno Hautanen Ulf R. Rapp 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》1984,803(3):153-162
Cultured epithelial rodent cells were transformed in vitro using ethylnitrosourea as a carcinogen either alone or in combination with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). The frequency of transformation in the absence of TPA was 5·10?4 at 10 μg/ml ethylnitrosourea. Growth of ethylnitrosourea-treated cells in TPA-substituted medium increased the transformation frequency 8-fold. Colonies of transformed cells were isolated from soft agar and analyzed for the production of pericellular matrix glycoproteins. The ethylnitrosourea-transformed cells retained pericellular matrix structures, typical of the nontransformed control cells. Parent cells produced into their culture media fibronectin and procollagen types I and III as their major pericellular glycoproteins. The ethylnitrosourea-transformed cells synthesized and secreted altered procollagen polypeptides. The procollagen of ethylnitrosourea-transformed cells apparently consisted mainly of homotrimeric proα1 molecules, with smaller amounts of basement membrane procollagen-like chains. Fibronectin synthesis or secretion was not affected by ethylnitrosourea-induced transformation, but the production of fibronectin was enhanced in the transformed cultures treated with TPA. Also, the deposition of procollagen and fibronectin into the pericellular matrix was not affected by ethylnitrosourea-transformation. Very similar changes had previously been observed in murine sarcoma virus-transformed cells. The change of procollagen type I thus appears to be a correlate of malignant transformation of cultured epithelial cells. The results indicate that ethylnitrosourea can induce malignant transformation of epithelial cells in culture and modify production and deposition of pericellular glycoproteins. 相似文献
159.
Aging of aqueous guaiacol (o-methoxyphenol) solutions over a period of several months led to the spontaneous formation of peroxidatic compound(s) and other unidentified oxidation products of guaiacol. This accelerated the oxidation of guaiacol catalyzed by lactoperoxidase (LPO) severalfold depending on the pH of the reaction mixture. The peroxide(s) acted like H2O2 while the aromatic oxidation products may be more reactive than guaiacol. Five- to 12-month-old 20 mm stock solutions contained even 0.05-0.3% of H2O2 equivalents. The formation of the peroxidatic compound(s) was found to be a photochemical process which progressed in a few hours at 254 nm and slowly (detectable in 2-week-old solutions) in regular glass bottles kept under normal laboratory illumination. The kinetics and pH dependence of the oxidation of aged guaiacol solutions by LPO were distinctly different from those found with fresh substrate. The spontaneously formed peroxidatic compound is possibly a better oxygen donor in LPO assays than H2O2. The spontaneously formed aromatic oxidation products of guaiacol may include compounds that contain diphenoquinone groups. The complexity of the oxidation of guaiacol and the multitude of reaction products formed require special consideration in kinetic studies of LPO. The use of 2,2′-azino-di(3-ethylbenzthiazoline-6-sulfonic acid) as a LPO substrate was studied. The published method utilizing this substrate was modified into a more sensitive procedure by readjusting some of the reaction conditions. 相似文献
160.
Fungicidal effect of human lactoferrin against Candida albicans 总被引:3,自引:0,他引:3
Human lactoferrin (LF) in its iron-free state (apo LF), killed Candida albicans in a time- and dose-dependent way. The lethal effect was stronger at pH 7.0 than at pH 5.5 and maximum inhibition at neutral pH was achieved in 25 min when the fungal cells were exposed to LF in 0.05 mM KCl at 37 degrees C. Fe(3+)-saturated LF had no fungicidal activity. Apo LF-mediated killing was also temperature-dependent with enhanced inhibition at higher temperatures (37 degrees, 42 degrees C). The presence of 1 mM D-glucose did not affect the candidacidal activity of apo LF but both phosphate and bicarbonate ions at physiological salivary concentrations completely blocked the anti-fungal effect. Therefore it seems unlikely that LF belongs to the major host defence factors against oral candidosis. 相似文献