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1. |
COMPARISON OF INDUCIBLE NITRIC OXIDE SYNTHASE GENE EXPRESSION AND LUNG INFLAMMATION FOLLOWING INTRATRACHEAL INSTILLATION OF SILICA, COAL, CARBONYL IRON, OR TITANIUM DIOXIDE IN RATS |
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Journal of Toxicology and Environmental Health,
Volume 51,
Issue 3,
1997,
Page 203-218
JohnA. Blackford,
William Jones,
RichardD. Dey,
Vincent Castranova,
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摘要:
The pulmonary toxicity of the respirable dusts silica, coal, carbonyl iron, and titanium dioxide on alveolar macrophage (AM) and neutrophil (PMN) inducible nitric oxide syn thase (iNOS) gene expression and nitric oxide (NO) production was investigated. Rats were intratracheal^ instilled with 5 mg/100 g body weight of silica, coal, carbonyl iron, or titanium dioxide. The dust particles averaged less than 5 pm in diameter. Bronchoalveolar lavage was performed 24 h later. Bronchoalveolar lavage cell (BALC) differentials, iNOS gene expression and NO production by BALC (measured indirectly as NO-dependent chemiluminescence), and lavageable lung protein levels were measured. Analyzed on an equal mass basis, silica, coal, and titanium dioxide dusts increased the production of iNOS-dependent NO by AM. Silica and titanium dioxide both increased the levels of iNOS mRNA while carbonyl iron and coal did not. Each dust caused an increase in PMN, indicating an inflammatory response. Carbonyl iron and titanium dioxide decreased the numbers of AM. Levels of acellular lavageable lung protein were increased by silica, car bonyl iron, and titanium dioxide. When exposure was normalized for an equal number of particles, the pneumotoxic dusts, silica and coal, caused more inflammation and NO pro duction than the nuisance dusts, carbonyl iron and titanium dioxide. Therefore, it appears that particle number is a more appropriate metric of exposure than mass when comparing the relative pathogenicity of dusts of different sizes. Furthermore, since the potency of these dusts (on a particle number basis) to increase iNOS gene expression reflects their inflammatory and pathogenic potential, it is proposed that NO may contribute to the early inflammatory damage observed in the lung following dust exposure.
ISSN:0098-4108
DOI:10.1080/00984109708984022
出版商:Taylor & Francis Group
年代:1997
数据来源: Taylor
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2. |
CHRONIC ULTRAVIOLET EXPOSURE-INDUCED p53 GENE ALTERATIONS IN SENCAR MOUSE SKIN CARCINOGENESIS MODEL |
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Journal of Toxicology and Environmental Health,
Volume 51,
Issue 3,
1997,
Page 219-234
Ying Tong,
MaryAnn Smith,
StephenB. Tucker,
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摘要:
Alterations of the tumor suppresser gene p53 have been found in ultraviolet radiation (UVR) related human skin cancers and in UVR-induced murine skin tumors. However, links between p53 gene alterations and the stages of carcinogenesis induced by UVR have not been clearly defined. We established a chronic UVR exposure-induced Senear mouse skin carcinogenesis model to determine the frequency of p53 gene alterations in different stages of carcinogenesis, including UV-exposed skin, papillomas, squamous-cell carcinomas (SCCs), and malignant spindle-cell tumors (SCTs). A high incidence of SCCs and SCTs were found in this model. Positive p53 nuclear staining was found in 10137 (27%) of SCCs and 12/24 (50%) of SCTs, but was not detected in normal skin or papillomas. DNA was isolated from 40 paraffin-embedded normal skin, UV-exposed skin, and tumor sections. The p53 gene (exons 5 and 6) was amplified from the sections by using nested polymerase chain reaction (PCR). Subsequent single-strand conformation polymorphism (SSCP) assay and sequencing analysis revealed one point mutation in exon 6 (coden 193, C → A transition) from a UV-exposed skin sample, and seven point mutations in exon 5 (codens 146, 158, 150, 165, and 161, three C → T, two C → A, one C → C, and one A → T transition, respectively) from four SCTs, two SCCs and one UV-exposed skin sam ple. These experimental results demonstrate that alterations in the p53 gene are frequent events in chronic UV exposure-induced SCCs and later stage SCTs in Senear mouse skin.
ISSN:0098-4108
DOI:10.1080/00984109708984023
出版商:Taylor & Francis Group
年代:1997
数据来源: Taylor
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3. |
DIFFERENTIAL INDUCTION OF POLYAMINE OXIDASE ACTIVITY IN LIVER AND HEART OF IRON-OVERLOADED RATS |
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Journal of Toxicology and Environmental Health,
Volume 51,
Issue 3,
1997,
Page 235-244
UlkaR. Tipnis,
Gui-Ying He,
M. Firoze Khan,
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摘要:
The present study was undertaken to investigate the effect of iron dextran treatment on polyamine oxidase (PAO) activity, iron accumulation, and lipid peroxidation in livers and hearts of rats. PAO catalyzes oxidative deamination of polyamines, the cellular aliphatic cations. This reaction produces highly toxic hydrogen peroxide, 3-acetamidopropanal, and precursors of higher polyamines. The rats were given iron dextran daily for 7 d. In iron-dextran-treated rats, a marked increase in the hepatic level of iron was associated with enhanced lipid peroxidation and increased PAO activity. Though iron accumulation and lipid peroxidation in the iron-treated rats increased significantly in the heart, PAO activity remained unchanged. The paraffin sections of livers stained with Perls iron stain showed the presence of iron in macrophages and hepatocytes. The sections of hearts showed iron deposits only in macrophages, while myocytes showed no iron staining. These results show that although iron dextran treatment results in accumulation of iron in both liver and heart, it induces PAO activity only in liver. The significance of increased PAO activity in lipid peroxidation and fibrosis in iron-mediated injury is discussed.
ISSN:0098-4108
DOI:10.1080/00984109708984024
出版商:Taylor & Francis Group
年代:1997
数据来源: Taylor
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4. |
INFLUENCE OF DIFFERENT DEGREES OF REDUCED RENAL MASS ON THE RENAL AND HEPATIC DISPOSITION OF ADMINISTERED CADMIUM |
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Journal of Toxicology and Environmental Health,
Volume 51,
Issue 3,
1997,
Page 245-264
RudolfsK. Zalups,
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摘要:
The present study was designed to evaluate, in rats, the effect of varying degrees of reduced renal mass on the disposition of administered cadmium. As part of this evalua tion, the intrarenal, hepatic, and hematological disposition of cadmium and the urinary and fecal excretion of cadmium were studied and characterized in control, uninephrec-tomized (NPX), and 75% nephrectomized (75% NPX) rats 1 d, 2 d, and 7 d after the intravenous injection of a nonnephrotoxic 8.9 μmol/kg dose of cadmium chloride. Renal accumulation of cadmium, especially in the cortex and outer stripe of the outer medulla, was reduced significantly in the 75% NPX rats, but not in the NPX rats, between d 2 and 7 after the injection of cadmium. The diminution in the renal accumulation of cadmium in the 75% NPX rats was most likely due to diminished glomerular filtration rate and renal clearance of cadmium induced by 75% nephrectomy. Despite reduced glomerular filtra tion rate, the cumulative urinary excretion of cadmium in the 75% NPX rats was signifi cantly greater than that in either the NPX rats or the control rats. It should be mentioned, however, that very little of the administered dose of cadmium was excreted in the urine by any of the three groups of rats. Interestingly, the content of cadmium in the liver was significantly greater in 75% NPX rats than in NPX or control rats between d 1 and 7 after the injection of cadmium. Moreover, the 75% NPX rats excreted significantly less cadmium in the feces over the 7 d of study than did the other 2 groups of rats, indicating that 75% nephrectomy causes a significant alteration in one or more of the mechanisms involved in the fecal excretion of cadmium. In summary, the findings from the present study indicate that the renal and hepatic handling of administered cadmium in rats changes significantly when renal mass is reduced by 75%. Further studies are needed to better characterize the effects of reductions of renal mass, which impair renal function significantly, on both the disposition and toxicity of cadmium in renal and hepatic tissues.
ISSN:0098-4108
DOI:10.1080/00984109708984025
出版商:Taylor & Francis Group
年代:1997
数据来源: Taylor
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5. |
SUBCHRONIC TOXICITY OF 2,2′,3,3′,4,4′-HEXACHLOROBIPHENYL IN RATS |
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Journal of Toxicology and Environmental Health,
Volume 51,
Issue 3,
1997,
Page 265-277
P. Lecavalier,
I. Chu,
A. Yagminas,
D. C. Villeneuve,
R. Poon,
M. Feeley,
H. Håkansson,
U. G. Ahlborg,
V. E. Valli,
Å. Bergman,
R. F. Seegal,
S. W. Kennedy,
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摘要:
The subchronic toxicity of 2,2′,3/3′,4,4′-hexachlorobiphenyl (PCB 128) was investigated in rats following dietary exposure at 0, 0.05, 0.5, 5, or 50 ppm for 13 wk. The growth rate was not affected by treatment and no apparent clinical signs of toxicity were observed. There was a significant increase in liver weight in the 50 ppm females. The liver ethoxy-resorufin deethylase (EROD) activity was increased by five- and fourfold in the highest dose males and females, respectively, while aminopyrine demethylase (ADPM) activity was significantly increased only in the highest dose females. Liver vitamin A was significantly reduced in the highest dose females. No other biochemical or hematological effects were observed. Treatment-related histopathological changes were seen in the thyroid and liver, and to a lesser extent in the bone marrow and thymus. Residue data showed a dose-dependent accumulation of PCB 128 in the following tissues: fat, liver, kidney, brain, spleen, and serum, with the highest concentration being found in fat followed by liver and kidney. Based on these data, the no-observable-adverse-effect level of PCB 128 was judged to be 0.5 ppm in diet or 42 yg/kg body weight.
ISSN:0098-4108
DOI:10.1080/00984109708984026
出版商:Taylor & Francis Group
年代:1997
数据来源: Taylor
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6. |
INFLUENCE OF DIETARY SELENIUM ON THE DISPOSITION OF ARSENATE IN THE FEMALE B6C3F1, MOUSE |
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Journal of Toxicology and Environmental Health,
Volume 51,
Issue 3,
1997,
Page 279-299
E. M. Kenyon,
M. F. Hughes,
O. A. Levander,
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摘要:
Interactions between arsenic (As) and selenium (Se) at the metabolic level are multi-faceted and complex. These interactions are of practical significance because populations in various parts of the world are simultaneously exposed to inorganic As in drinking water and Se mainly in the diet at varying levels. The primary goal of this study was to investi gate whether differing dietary Se status would alter the profile of urinary metabolites or their time course for elimination after exposure to arsenate [As(V)]. Weanling female B6C3F, mice were maintained for 28 d on either a control diet of powdered rodent meal sufficient in Se (A, 0.2 ppm) or Torula yeast-based (TYB) diets deficient (B, 0.02 ppm Se), sufficient (C, 0.2 ppm Se), or excessive (D, 2.0 ppm Se) in Se; mice then received by oral gavage 5 mg (As)/kg as sodium [73As] arsenate. The time course for elimination of total arsenic and metabolites in urine was measured over a 48-h period, and total arsenic was determined in feces and tissues at 48 h. Mice on the Se excess diet excreted a signifi cantly higher percentage of urinary As as inorganic As, with a significantly decreased ratio of organic to inorganic As compared to Se-sufficient mice, suggesting that As methylation was decreased. Mice on the Se-deficient diet appeared to eliminate As(V), arsenite, and dimethylarsinic acid (DMA) in urine more slowly than Se-sufficient mice; however, further studies are required to confirm this finding. Mice on the Se-sufficient meal diet (A) excreted significantly less (by percent) arsenate-derived radioactivity in urine and more in feces compared to mice on the Se-sufficient TYB diet (C), with total elimination being similar for both groups. This indicates that mice on the meal diet absorbed significantly less As(V) than mice on the TYB diet, and this may be due to more fiber or “bulk” in the meal diet.
ISSN:0098-4108
DOI:10.1080/00984109708984027
出版商:Taylor & Francis Group
年代:1997
数据来源: Taylor
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7. |
A Review of: “EXPERIMENTAL TOXICOLOGY: THE BASIC ISSUES” Edited by D. Anderson and D. M. Conning Royal Society of Chemistry, Cambridge, UK, 1993, viii-566 pp. |
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Journal of Toxicology and Environmental Health,
Volume 51,
Issue 3,
1997,
Page 301-303
RamP. Gupta,
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ISSN:0098-4108
DOI:10.1080/00984109708984028
出版商:Taylor & Francis Group
年代:1997
数据来源: Taylor
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