Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 16 de 16
Filter
Add more filters










Publication year range
1.
Sci Rep ; 12(1): 139, 2022 01 07.
Article in English | MEDLINE | ID: mdl-34996936

ABSTRACT

Occupational exposure of anticancer agents during their preparation has been recognized as a serious hazard. Closed system drug transfer devices (CSTDs) enable "safe" preparation of agents for medical personnel and ensure a safe hospital environment. However, artificial particles of infusion materials have been reported during CSTD use. Here, the incidence of insoluble fine particles during preparation of anticancer agents using CSTDs was examined. Visible insoluble fine particles were found in 465 (9.4%) of 4948 treatment cases at Ehime University Hospital with CSTD use. Contaminants occurred more frequently during preparation of monoclonal antibodies than cytotoxic anticancer agents (19.4% vs. 4.1%, respectively, P < 0.01). A similar survey was conducted at nine hospitals to investigate the incidence of insoluble fine particles with or without CSTDs. Insoluble fine particles were detected in 113 (15.4%) of 732 treatment cases during preparation of monoclonal antibodies with CSTD use. In contrast, the occurrence of insoluble fine particles without CSTDs was found in only 3 (0.073%) of 4113 treatment cases. Contamination with CSTDs might cause harmful effects on patients during cancer therapy. We strongly recommend the use of in-line filters combined with infusion routes after CSTD use to avoid contamination-associated adverse events.


Subject(s)
Antibodies, Monoclonal/analysis , Antineoplastic Agents/analysis , Chemical Safety/instrumentation , Equipment Contamination , Hazardous Substances/analysis , Occupational Exposure/analysis , Protective Devices , Antibodies, Monoclonal/adverse effects , Antineoplastic Agents/adverse effects , Drug Compounding , Equipment Contamination/prevention & control , Hazardous Substances/adverse effects , Health Personnel , Hospitals , Humans , Injections , Japan , Occupational Exposure/prevention & control , Occupational Health , Patient Safety , Risk Assessment
2.
J Toxicol Sci ; 43(2): 113-127, 2018.
Article in English | MEDLINE | ID: mdl-29479033

ABSTRACT

The carcinogenicity of quinoline was examined by administrating quinoline in the drinking water to groups of 50 F344/DuCrj rats and 50 Crj: BDF1 mice of each sex. In rats, the doses of quinoline were 0, 200, 400, and 800 ppm for males and 0, 150, 300, and 600 ppm for females. In male rats, administration of quinoline was terminated at week 96 due to high mortality caused by tumors. There were significant increases of hepatocellular adenomas, hepatocellular carcinomas, hepatocellular adenomas and/or carcinomas (combined), and liver hemangiomas, hemangiosarcomas, hemangiomas and/or hemangiosarcomas (combined) in both male and female rats, and nasal esthesioneuroepitheliomas and sarcoma NOS (not otherwise specified) in males. In mice, doses of quinoline were 0, 150, 300 and 600 ppm for both males and females. Administration of quinoline was terminated at week 65 in males and at week 50 in females due to high mortality caused by tumors. There were marked increases of hemangiomas, hemangiosarcomas, and hemangiomas and/or hemangiosarcomas (combined) in the retroperitoneum, mesenterium, and liver in males, and in the retroperitoneum, mesenterium, peritoneum, and subcutis in females. Additionally, histiocytic sarcomas were statistically increased in the livers of female mice. Thus the present studies provided clear evidence of carcinogenic activity of quinoline administered in the drinking water in both rats and mice.


Subject(s)
Drinking Water/administration & dosage , Neoplasms/chemically induced , Quinolines/administration & dosage , Quinolines/toxicity , Administration, Oral , Animals , Carcinoma, Hepatocellular/chemically induced , Female , Hemangiosarcoma/chemically induced , Liver Neoplasms/chemically induced , Male , Mice, Inbred Strains , Mutagenesis/drug effects , Rats, Inbred F344 , Specific Pathogen-Free Organisms
3.
J Toxicol Sci ; 38(6): 913-24, 2013.
Article in English | MEDLINE | ID: mdl-24213011

ABSTRACT

Ethyl tertiary-butyl ether (ETBE) is an oxygenated gasoline additive synthesized from ethanol and isobutene that is used to reduce CO2 emissions. To support the Kyoto Protocol, the production of ETBE has undergone a marked increase. Previous reports have indicated that exposure to ETBE or methyl tertiary-butyl ether resulted in liver and kidney tumors in rats and/or mice. These reports raise concern about the effects of human exposure being brought about by the increased use of ETBE. The present study was conducted to evaluate the genotoxicity of ETBE using micronucleus induction of polychromatic erythrocytes in the bone marrow of male and female rats treated with ETBE in the drinking-water at concentrations of 0, 1,600, 4,000 or 10,000 ppm or exposed to ETBE vapor at 0, 500, 1,500 or 5,000 ppm for 13 weeks. There were no significant increases in micronucleus induction in either the drinking water-administered or inhalation-administered groups at any concentration of ETBE; although, in both groups red blood cells and hemoglobin concentration were slightly reduced in the peripheral blood in rats administered the highest concentration of ETBE. In addition, two consecutive daily intraperitoneal injections of ETBE at doses of 0, 250, 500 or 1,000 mg/kg did not increase the frequency of micronucleated bone marrow cells in either sex; all rats receiving intraperitoneal injections of ETBE at a dose of 2,000 mg/kg died after treatment day 1. These data suggest that ETBE is not genotoxic in vivo.


Subject(s)
Bone Marrow Cells/cytology , Bone Marrow Cells/drug effects , Ethyl Ethers/administration & dosage , Ethyl Ethers/toxicity , Micronuclei, Chromosome-Defective/drug effects , Micronucleus Tests , Administration, Oral , Animals , Bone Marrow , Dose-Response Relationship, Drug , Drinking Water , Female , Gasoline , Inhalation Exposure , Injections, Intraperitoneal , Male , Rats , Rats, Inbred F344
4.
Arch Toxicol ; 87(5): 905-14, 2013 May.
Article in English | MEDLINE | ID: mdl-23389738

ABSTRACT

Carcinogenicity of ethyl tertiary-butyl ether (ETBE) was examined with inhalation exposure using F344/DuCrlCrlj rats. Groups of 50 male and 50 female rats, 6 week old at commencement, were exposed to ETBE at 0, 500, 1,500 or 5,000 ppm (v/v) in whole-body inhalation chambers for 6 h/day, 5 days/week for 104 weeks. A significant increase in the incidence of hepatocellular adenomas was indicated in males exposed at 5,000 ppm, but not in females at any concentration. In addition, significantly increased incidences of eosinophilic and basophilic cell foci were observed in male rats at 5,000 ppm. Regarding non-neoplastic lesions, rat-specific changes were observed in kidney, with an increase in the severity of chronic progressive nephropathy in both sexes at 5,000 ppm. Increased incidences of urothelial hyperplasia of the pelvis were observed at 1,500 ppm and above, and mineral deposition was apparent in the renal papilla at 5,000 ppm in males. There were no treatment-related histopathological changes observed in any other organs or tissues in either sex. The present 2-year inhalation study demonstrated hepatotumorigenicity of ETBE in male, but not in female rats.


Subject(s)
Adenoma/chemically induced , Air Pollutants/toxicity , Carcinogens/toxicity , Ethyl Ethers/toxicity , Liver Neoplasms/chemically induced , Adenoma/pathology , Animals , Carcinogenicity Tests , Chronic Disease , Female , Inhalation Exposure , Kidney/drug effects , Kidney/pathology , Kidney Diseases/chemically induced , Kidney Diseases/pathology , Liver Neoplasms/pathology , Male , Rats , Rats, Inbred F344 , Sex Factors
5.
J Occup Health ; 53(3): 175-87, 2011.
Article in English | MEDLINE | ID: mdl-21471693

ABSTRACT

OBJECTIVES: Carcinogenicity and chronic toxicity of indium-tin oxide (ITO) were examined by inhalation exposure of rats and mice to ITO aerosol. METHODS: Fifty mice of both sexes were exposed to ITO at 0 (control), 0.01, 0.03 or 0.1 mg/m(3) for 6 h/day, 5 day/wk for 104 wk, and 50 rats of both sexes were exposed to 0, 0.01 or 0.03 mg/m(3) ITO for the same time period. The repeated exposure of 50 rats of both sexes to 0.1 mg/m(3) ITO was discontinued at the 26th wk, followed by clean air exposure for the remaining 78 wk. RESULTS: In rats, incidences of bronchiolo-alveolar adenomas and carcinomas, bronchiolo-alveolar hyperplasia, alveolar wall fibrosis and thickened pleural wall, alveolar proteinosis and infiltrations of alveolar macrophages and inflammatory cells were significantly increased. Combined incidences of malignant lung tumors in male rats and total lung tumors in male and female rats were significantly increased at exposure to 0.01 mg/m(3) ITO. In mice, no carcinogenic response occurred, but thickened pleural wall, alveolar proteinosis and alveolar macrophage infiltration were induced. Mice were less susceptible to ITO than rats. The lung content of indium was the greatest, followed by the spleen, kidney and liver. Blood indium levels increased dose-dependently. CONCLUSIONS: There was clear evidence of carcinogenicity of inhaled ITO in male and female rats but not clear evidence in mice, together with occurrence of the chronic pulmonary lesions in both rats and mice.


Subject(s)
Lung Neoplasms/chemically induced , Lung Neoplasms/epidemiology , Lung/drug effects , Lung/pathology , Tin Compounds/toxicity , Adenocarcinoma, Bronchiolo-Alveolar/chemically induced , Adenocarcinoma, Bronchiolo-Alveolar/epidemiology , Adenoma/chemically induced , Adenoma/epidemiology , Aerosols , Animals , Carcinogenicity Tests , Female , Inhalation Exposure/adverse effects , Male , Mice , Rats , Rats, Inbred F344 , Survival Analysis , Tin Compounds/blood , Tin Compounds/urine
6.
J Occup Health ; 53(3): 234-9, 2011.
Article in English | MEDLINE | ID: mdl-21422720

ABSTRACT

OBJECTIVES: Inhalation toxicities of indium-tin oxide (ITO) and indium oxide (IO) in mice were characterized in comparison with those previously reported in rats. METHODS: B6C3F(1) mice of both sexes were exposed by inhalation to ITO or IO aerosol for 6 h/day, 5 day/wk for 2 wk at 0, 0.1, 1, 10 or 100 mg/m(3) or 13 wk at 0, 0.1or 1 mg/m(3). RESULTS: ITO and IO particles were deposited in the lung, mediastinal lymph node (MLN) and nasal-associated lymphoid tissue. Alveolar proteinosis, infiltrations of alveolar macrophages and inflammatory cells and increased lung weight were induced by 2- and 13-week exposures to ITO and IO, while alveolar epithelial hyperplasia occurred only in the 2-week exposures. Thickened pleural wall, hyperplastic MLN, extramedullary hematopoiesis in the spleen and increased levels of erythrocyte parameters were induced by 13-week exposure to ITO. The ITO- and IO-induced pulmonary lesions were milder in mice than those previously reported in rats, and the fibrotic lesions were different between these two species. Indium levels in the lung and pooled blood were analyzed in the mice exposed to ITO and IO for 13 wk. In the 13-week inhalation exposure of mice to ITO, alveolar proteinosis and significantly increased lung weight were induced at the same exposure concentration as the current threshold limit value for indium and its compounds.


Subject(s)
Indium/toxicity , Lung/drug effects , Lung/pathology , Pulmonary Alveolar Proteinosis/chemically induced , Tin Compounds/toxicity , Aerosols , Animals , Female , Indium/blood , Indium/urine , Inhalation Exposure , Macrophages, Alveolar/drug effects , Male , Mice , Pulmonary Alveolar Proteinosis/pathology , Spleen/drug effects , Spleen/pathology , Tin Compounds/blood , Tin Compounds/urine
7.
J Mol Endocrinol ; 45(5): 329-40, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20801894

ABSTRACT

This study was undertaken to elucidate the effects of dietary protein deprivation on glucose metabolism and hepatic insulin signaling in rats. The results of glucose and pyruvate tolerance tests in rats fed with a 12% casein diet (12C) and a protein-free diet (PF) indicated that protein deprivation enhanced clearance of blood glucose and suppressed gluconeogenesis. Correspondingly, the mRNA level of hepatic phosphoenolpyruvate carboxykinase, a key gluconeogenic enzyme, was suppressed by dietary protein deprivation. In PF-fed rats, total tyrosine phosphorylation of insulin receptor (IR) in the liver induced by insulin injection was enhanced compared with 12C pair-fed rats due to an increase in IR protein level. In addition, protein deprivation caused an increase in protein levels of IR substrate 1 (IRS1) and IRS2, leading to the marked enhancement of insulin-induced tyrosine phosphorylation of IRS2 and its binding to the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3K). Based on these results, we conclude that protein deprivation suppresses gluconeogenesis by a mechanism primarily mediated by the enhancement of the insulin signals through the IR/IRS/PI3K/mammalian target of rapamycin complex 1 pathway in the liver. Taken together with our previous report, these findings suggest that tissue-specific potentiation of insulin action in the liver and the skeletal muscle plays important roles in maintaining glucose homeostasis even when energy usage is reduced by dietary protein deprivation.


Subject(s)
Diet, Protein-Restricted/adverse effects , Dietary Proteins/administration & dosage , Gluconeogenesis , Insulin/metabolism , Liver/metabolism , Animals , Blood Glucose/metabolism , Dietary Proteins/pharmacology , Energy Metabolism , Homeostasis/physiology , Insulin/blood , Insulin/pharmacology , Insulin Receptor Substrate Proteins/metabolism , Liver/drug effects , Liver/enzymology , Male , Phosphatidylinositol 3-Kinase/metabolism , Phosphorylation , Protein Deficiency/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Wistar , Receptor, Insulin/genetics , Receptor, Insulin/metabolism , Signal Transduction/drug effects , TOR Serine-Threonine Kinases/metabolism , Up-Regulation
8.
Gan To Kagaku Ryoho ; 35(6): 961-4, 2008 Jun.
Article in Japanese | MEDLINE | ID: mdl-18633225

ABSTRACT

We encountered a 64-year-old UGT1A1*28 heterotype patient who received CPT-11 and CDDP chemotherapy for Stage III A small-cell lung-cancer and developed grade 4 neutropenia as assessed by CTCAE v3.0 in Pharmaceutical Management. The therapeutic effect was good; 4 courses of chemotherapy could be safely administered at 1/3 of the applied dose of CPT-11, and CR was obtained. In this period, we participated in selecting antibiotics to neutropenia and CPT-11 closing regimen as pharmacists. Additionally, we carefully monitored patients about their bowel pattern and hematotoxicity, and collected information about gene searching for the patient and the Hospital Ethics Committee. The analysis of the gene polymorphism of CPT-11 is useful to predict the occurrence of serious side effects, but this judgment cannot easily be made clinically. In the event of a marked decrease in the neutrophil count of a patient during the first courses of treatment with CPT-11, we believe that it is important to consider gene polymorphism, to closely monitor the symptoms and laboratory parameters, and to give a smaller dose of the drug.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Camptothecin/analogs & derivatives , Carcinoma, Small Cell/drug therapy , Carcinoma, Small Cell/pathology , Cisplatin/therapeutic use , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Camptothecin/therapeutic use , Carcinoma, Small Cell/diagnostic imaging , Humans , Irinotecan , Lung Neoplasms/diagnostic imaging , Male , Middle Aged , Radiography , Remission Induction , Time Factors
9.
Biosci Biotechnol Biochem ; 71(5): 1334-7, 2007 May.
Article in English | MEDLINE | ID: mdl-17485842

ABSTRACT

The production of insulin-like growth factor-binding protein-1 (IGFBP-1) in HepG2 was increased by cadmium cation (Cd2+) at 3 microM, but not by other divalent cations. The mRNA level of IGFBP-1 was also increased by the administration of 3 microM of Cd(2+). These results suggest that Cd(2+) impacts the gene expression of IGFBP-1, which leads to production of IGFBP-1.


Subject(s)
Cadmium/pharmacology , Carcinoma, Hepatocellular/metabolism , Insulin-Like Growth Factor Binding Protein 1/biosynthesis , Liver Neoplasms/metabolism , RNA, Messenger/metabolism , Carcinoma, Hepatocellular/pathology , Cations/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Dose-Response Relationship, Drug , Formazans/metabolism , Humans , Liver Neoplasms/pathology , Tetrazolium Salts/metabolism , Time Factors
10.
J Toxicol Sci ; 32(1): 47-56, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17327693

ABSTRACT

Dose- and time-dependent effects of 2,3,7,8-tetrabromodibenzo-p-dioxin (TBDD) on the liver were examined by single administration of TBDD by gavage to male and female rats. Fifteen Wistar rats of each sex per group received 0, 10, 30, 100 or 300 microg TBDD/kg body weight. Rats surviving to scheduled necropsy on Day 2, 7 or 36 after the TBDD administration were examined for hepatic histopathology, activities of hepatic microsomal enzymes and serum levels of lipids, total cholesterol and transaminases and hepatic concentrations of TBDD. Tigroid basophilic cytoplasm and hepatocellular hypertrophy were observed at 10 microg/kg on Day 2 or 7 through 36, whereas degenerative and aggressive lesions such as necrosis, fibrosis, multinucleated hepatocytes and disarrangement of hepatocytes occurred later at higher dose levels. Persistently increased activities of hepatic aryl hydrocarbon hydroxylase (AHH), ethoxycoumarin O-deethylase (ECOD) and ethoxyresorufin O-deethylase (EROD), increased serum levels of total cholesterol and phospholipid and increased relative liver weight were observed in all groups dosed 10 mug/kg and above, suggesting that hepatic microsomal monooxygenases and basophilic cytoplasm of hepatocytes were early and sensitive indicators among those TBDD-induced effects. A dose-dependent increase in liver concentrations of TBDD on Day 2 was followed by logarithmic decreases in TBDD concentrations against the days elapsed after the TBDD administration. An elimination half-life (t(1/2)) of TBDD from the liver was estimated to range from 12 to 16 days. It was suggested that females were more susceptible to TBDD than males, and that acute hepatotoxicity of TBDD was as potent as that of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).


Subject(s)
Chemical and Drug Induced Liver Injury , Dioxins/administration & dosage , Dioxins/toxicity , Liver/drug effects , Animals , Dioxins/pharmacokinetics , Dose-Response Relationship, Drug , Female , Liver/enzymology , Male , Rats , Rats, Wistar , Sex Factors
11.
Environ Health Prev Med ; 11(3): 136-44, 2006 May.
Article in English | MEDLINE | ID: mdl-21432388

ABSTRACT

OBJECTIVE: Systemic and myelotoxic effects of 2,3,7,8-tetrabromodibenzo-p-dioxin (TBDD) were examined by the single administration of TBDD by gavage to rats. METHODS: Fifteen Wistar rats of both sexes per group received 0, 10, 30, 100 or 300 µg TBDD/kg body weight. Rats surviving to the scheduled necropsy on Days 2, 7 and 36 after TBDD administration were examined for growth rate, organ weight, hematology, histopathology and adipose tissue levels of TBDD. RESULTS: Three 300 µg/kg-dosed females died on Days 21, 23 and 27, and exhibited a marked decrease in body weight, severe thymic atrophy, decreased bone marrow hematopoiesis and hemorrhage in the subarachnoid space of brain and spinal cord. TBDD-dosed surviving rats exhibited growth retardation, decreased bone marrow hematopoiesis, decreases in red blood cell counts, hemoglobin concentrations, and hematocrit values, an increase in reticulocytes and decreases in platelet counts, white blood cell counts and eosinophils. These signs suggested TBDD myelotoxicity. Splenic extramedullary hematopoiesis was increased in both sexes given TBDD, whereas atrophy of the splenic white pulp occurred only in TBDD-dosed females. Marked decreases in body weights and the size and weight of the thymus, severe thymic atrophy and death in TBDD-dosed females suggested a wasting syndrome. The adipose tissue level of TBDD culminated on Day 7 and decreased to 20-30% of the Day 7 level on Day 36. CONCLUSIONS: The TBDD-induced effects were characterized by a wasting syndrome and myelotoxicity that appeared at the dose levels of 30 µg/kg and higher and caused death in 300 µg/kg-dosed females.

12.
Biosci Biotechnol Biochem ; 67(4): 736-42, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12784612

ABSTRACT

The status of hyaluronan, the major glycosaminoglycan in the skin, is regulated by many factors such as cytokines and glucocorticoids. To examine whether and how protein malnutrition affects the status of skin hyaluronan, the hyaluronan content and mRNA levels of hyaluronan synthases (has) were analyzed in the skin of rats fed on a protein-free diet or on a 12% gluten diet. When these malnourishing diets had been given for 1 week, the hyaluronan content was significantly reduced as compared with that in rats fed on a 12% casein diet. Substantial falls in the mRNA levels of rhas2 and rhas3 were also observed. The reduction of mRNAs was already evident on the second day of treatment with the malnourishing diets. These results suggest that protein malnutrition has a primary impact on the gene expression of rhass, which leads to the reduction of hyaluronan content and to disfunction of the skin.


Subject(s)
Dietary Proteins/pharmacology , Gene Expression Regulation, Enzymologic/drug effects , Glucuronosyltransferase/genetics , Glycosyltransferases , Membrane Proteins , Skin/enzymology , Transferases , Xenopus Proteins , Animals , Caseins/pharmacology , Glucuronosyltransferase/analysis , Hyaluronan Synthases , Hyaluronic Acid/analysis , Male , Nutritional Physiological Phenomena , Polymerase Chain Reaction , RNA, Messenger/analysis , Rats , Rats, Wistar , Skin/chemistry
13.
Mutat Res ; 518(1): 39-45, 2002 Jun 27.
Article in English | MEDLINE | ID: mdl-12063065

ABSTRACT

The in vivo micronucleus test using mouse colonic epithelial cells was evaluated as the 11th collaborative study organized by the Collaborative Study Group on the micronucleus test (CSGMT) with three model chemicals that were known to induce chromosome damage in mouse colonic cells. Five laboratories participated in this validation study. All three model chemicals, i.e. 1,2-dimethylhydrazine dihydrochloride (1,2-DMH), N-methyl-N-nitrosourea (MNU), and mitomycin C (MMC), induced micronucleated colonic epithelial cells in a 4-day exposure protocol in all participating laboratories. We confirmed that the present single cell suspension method could be used to detect the model chemicals as micronucleus inducers in mouse colonic epithelial cells. Advantages of this method are that experiments are easy to perform and that intact cells can be analyzed. The present study suggested that the colon micronucleus assay proposed here is useful for mechanistic studies of colon carcinogenesis.


Subject(s)
Colon/drug effects , Micronucleus Tests/methods , Mutagens/toxicity , 1,2-Dimethylhydrazine/administration & dosage , 1,2-Dimethylhydrazine/toxicity , Animals , Colonic Neoplasms/etiology , Dose-Response Relationship, Drug , Epithelial Cells/drug effects , Male , Methylnitrosourea/administration & dosage , Methylnitrosourea/toxicity , Mice , Mice, Inbred ICR , Mitomycin/administration & dosage , Mitomycin/toxicity , Mutagens/administration & dosage
14.
Biosci Biotechnol Biochem ; 66(1): 117-26, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11866093

ABSTRACT

Protein malnutrition affects the status of dermal collagen, the major structural protein in the skin. However, the molecular mechanism underlying the alteration of collagen fibers in the skin by protein deficiency remains unknown. In the present study, the effect of dietary protein deprivation on collagen metabolism was studied by analyzing the status of the synthesis and degradation of collagen in the dorsal skin of rats. Feeding on a protein-free diet for 8 days caused a dramatic decrease in both types I and III tropocollagen with a concomitant decrease in their mRNA levels, with type III collagen being more severely affected. The active form of collagenase was significantly decreased by protein deprivation, whereas the latent form was not affected. The mRNA levels of collagenase and its inhibitors (TIMP-1 and 2) were also decreased by protein deprivation. These results suggest that both the synthesis and degradation of types I and III collagen were affected by protein deficiency.


Subject(s)
Collagen Type III/metabolism , Collagen Type I/metabolism , Dietary Proteins/metabolism , Skin/metabolism , Animals , Collagen Type I/genetics , Collagen Type III/genetics , Collagenases/genetics , Collagenases/metabolism , Deficiency Diseases , Food Deprivation , Gene Expression , Male , RNA, Messenger , Rats , Rats, Wistar , Tissue Inhibitor of Metalloproteinase-1/genetics , Tissue Inhibitor of Metalloproteinase-2/genetics , Tissue Inhibitor of Metalloproteinase-3/genetics
15.
J Biol Rhythms ; 17(1): 14-27, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11837944

ABSTRACT

The circadian system is thought to have three components: input, pacemaker (internal clock), and output. Cryptochromes (Cry) are important clock genes, and recent findings indicate that these genes not only act as circadian photoreceptors but are also essential components in the negative feedback of the circadian system. As a first step toward understanding the avian circadian system, the authors tried to clone Japanese quail homologs of mammalian Crys and analyze their expression patterns in different circumstances. Partial cDNAs of qCry1 and qCry2, which are homologs of mammalian Cry1 and Cry2, respectively, were obtained and their gene expressions were analyzed. Both qCry1 and qCry2 mRNAs were present in all the tissues examined. The oscillation patterns of the qCry1 transcripts were tissue specific and generally showed robust changes between daytime and nighttime; except for lung and testis tissues (which showed no detectable changes between daytime and nighttime), daytime levels were higher in all of the tissues examined. This rapid oscillation in qCry1 persisted through constant darkness or constant illumination, indicating that an endogenous clock controls these changes. In contrast, the expression of qCry2 did not oscillate in any tissue examined. In addition, in tissues of the pineal gland and eye, unexpected light exposure in the dark period was able to block the decrease in qCry1 transcripts or induce its expression. These findings, in conjunction with the established roles of CRYs in other species, led the authors to propose that in the circadian system, qCRYs may play important roles similar to the known roles of CRYs of other species, such as acting as circadian photoreceptors and as components of the circadian system.


Subject(s)
Circadian Rhythm/genetics , Coturnix/genetics , Coturnix/physiology , Drosophila Proteins , Eye Proteins , Flavoproteins/genetics , Gene Expression Regulation/physiology , Photoreceptor Cells, Invertebrate , Amino Acid Sequence , Animals , Cloning, Molecular , Cryptochromes , DNA, Complementary/biosynthesis , DNA, Complementary/genetics , Eye/metabolism , Lighting , Male , Molecular Sequence Data , Nuclease Protection Assays , Pineal Gland/metabolism , Receptors, G-Protein-Coupled , Tissue Distribution
16.
J Nutr Sci Vitaminol (Tokyo) ; 48(6): 453-60, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12775111

ABSTRACT

Vitamin A (VA) and insulin-like growth factors (IGF) are important regulators of a wide range of physiological processes. To investigate the IGF system's involvement in the physiological actions of VA, we examined the effects of VA status on components of the IGF system in rats. Male rats (3-wk-old) fed a VA-deficient diet for 11 wk developed VA deficiency, as confirmed by the depletion of serum retinol and hepatic retinyl palmitate. Rats fed the VA-deficient diet had significantly lower body weight (p < 0.05) and lower serum IGF-I concentrations than the rats fed the control diet. The decreases in serum IGF-I levels were accompanied by approximately 40% lower levels of the IGF-I mRNA in the liver and lungs. With respect to the gene expression of other IGF system components, VA deficiency caused a twofold induction of IGF-I receptor (IGF-IR) mRNA in the heart and a twofold reduction in IGFBP-6 mRNA in the lungs, but did not alter the expression of IGF-II, IGFBP-1, IGFBP-3, IGFBP-4 or IGFBP-5 in all tissues examined. When VA-deficient rats received a single injection of retinoic acid (2 mg/rat), tissue IGF-I and IGF-IR gene expression did not change after 4 or 8 h, while the expression of IGF-II, IGFBP-4, and IGFBP-6 mRNAs in some tissues increased rapidly. These results suggest a possible involvement of the IGF system in mediating the physiological actions of VA, including VA-supported growth, in the rat.


Subject(s)
Insulin-Like Growth Factor Binding Proteins/metabolism , Somatomedins/metabolism , Vitamin A Deficiency/metabolism , Vitamin A/analogs & derivatives , Vitamin A/metabolism , Animals , Blotting, Northern , Diterpenes , Gene Expression Regulation , Insulin-Like Growth Factor Binding Proteins/biosynthesis , Insulin-Like Growth Factor Binding Proteins/genetics , Male , RNA, Messenger/chemistry , RNA, Messenger/genetics , Random Allocation , Rats , Rats, Wistar , Retinyl Esters , Somatomedins/biosynthesis , Somatomedins/genetics , Tissue Distribution , Tretinoin/metabolism , Vitamin A/administration & dosage , Vitamin A/blood , Vitamin A Deficiency/genetics
SELECTION OF CITATIONS
SEARCH DETAIL
...