摘要:

The metallothionein-IIAgene (MT-IIA) is a major member of the human MT gene family. Metallothioneins (MTs) are low-molecular-weight, cysteine-rich proteins that bind and detoxify heavy metals. At least two different MT-IIApolymorphisms have been identified in humans, one or both of which may affect susceptibility to metal toxicity. The purpose of this study was to investigate whether these different genotypes affect the inducibility of MT-IIAmRNA in human lymphocytes treated with zinc (Zn), the major known inducer of MT-IIAin vitro. Fresh lymphocytes obtained from 16 healthy volunteers, aged 23-38 yr, were genotyped for the MT-IIAgene and tested for expression. A 435-bp Hin dIII- Taq I fragment of the MT-IIApromoter was used to probe for the two knownpolymorphisms (a 7.8-kb vs. a 5.3-kb fragment, and a 1.7-kb vs. a 1.6-kb fragment). The allele frequencies of the 16 subjects were 14% for 5.3-kb allele and 19% for 1.6-kb allele. In Northern blotting experiments, MT-IIAmRNA levels were induced over a wide range of Zn concentrations during 2-h exposures; specifically, levels increased by 9- to 115-fold with exposure to 100 µ M ZnCl2and by 16- to 311-fold with exposure to 200 µ M ZnCl2. However, no significant differences in MT-IIAinducibility were found between the 7.8/5.3 -kb allele pair (n = 4) and the 7.8/7.8 -kb allele pair (n = 12) or between the 1.7/1.6 -kb allele pair (n = 5) and the 1.7/1.7 -kb allele pair (n = 11). Thus, MT-IIAis strongly inducible by Zn in human lymphocytes, but individual variations exceed those that can be attributed to the known promoter-region polymorphisms.

ISSN:1528-7394    

DOI:10.1080/00984100050194081

出版商:Informa UK Ltd    

年代:2000

数据来源: Taylor

摘要:

The aim of this study was to investigate the effects of chronic, daily, 30-d administration of manganese chloride (MnCl2) to male Sprague-Dawley rats on lipid peroxidation in various tissues. Rats were intraperitoneally injected with MnCl2(20 mg/kg) once daily for 30 con secutive days. The Mn accumulated in liver, spleen, adrenal glands, heart, kidneys, lung, and testes. This was associated with decreased lipid peroxidation in liver, spleen, and adrenal glands and a decrease in the levels of Fe in these tissues. In a second group of animals, Mn (20 mg/kg/d) and glutathione (GSH, 15 mg/kg/d) were administered ip for 30 d. GSH counteracted the Mn-induced protective fall in lipid peroxidation, but Fe levels remained lower in liver and spleen. Mn decreases lipid peroxidation in certain tissues, which may involve lowering Fe content, but interaction with Fe is not the sole mechanism.

ISSN:1528-7394    

DOI:10.1080/00984100050194090

出版商:Informa UK Ltd    

年代:2000

数据来源: Taylor

摘要:

About 10 million industrial workers of both sexes are exposed to metal-working fluids (MWFs) via inhalation, skin or both. Our preliminary results, following dermal application of 200 µl of 50% unused (neat) semisynthetic MWF (pH 7 or pH 9.7) to the unshaved backs of 6-wk-old B6C3F1 mice, twice a week for 6 wk, produced significant increase in weights of the liver of both sexes. The purpose of the present study was to determine if this weight change was related to oxidative stress subsequent to MWF exposure and also to determine whether ethanol intake influences this effect. Therefore, 6-mo-old mice of both sexes were exposed to MWFs following the protocol just described, except that the topical application was with 5% MWFs (pH 7 and 9.7, 5 d/wk) with or without adding 5% ethanol to their drinking water (7 d/wk) for 13 wk. The skin histamine levels and mast-cell numbers were significantly increased in the female group treated with 5% MWF (pH 7). The ascorbic acid levels in the liver (both sexes) (all groups except 5% MWF pH 9.7 males) and testes were reduced significantly. Malondialdehyde levels in the male liver were significantly increased with topical MWF exposure. Glutathione levels were reduced significantly in both male and female liver after 5% MWF (pH 7). Alcohol dehydrogenase activity of the male liver increased significantly after MWF (pH 7). These results suggest that MWFs are absorbed through the skin and produce toxicity in the liver of both sexes and in the male gonads. This may represent an important health risk to MWF-exposed industrial workers, and ethanol may exacerbate this risk.

ISSN:1528-7394    

DOI:10.1080/00984100050194108

出版商:Informa UK Ltd    

年代:2000

数据来源: Taylor

摘要:

This study examined the effects of simultaneous exposure to saline and cadmium (Cd) on organ mass and histology of a bird with salt glands, the Pekin duck, Anas platyrhynchos. Three mixed-sex groups, each containing 6 birds, ate duck pellets containing 0, 50, or 300 µg Cd/g, respectively, for 4½ mo and drank 300 m M NaCl. Only females on the high-Cd diet lost body mass. Ingestion of Cd reduced heart mass in females. There was increased mass of Harderian and salt glands in both sexes. Mass of kidneys and liver increased only in males, and the gut mass (also length) increased more in males. Cadmium ingestion also induced (1) inflammation of renal interstitium and degenerative tubular changes, (2) marked degenerative changes in testes, (3) increased heart water content, (4) decreased cytoplasmic volume of liver cells, (5) reduced proportion of basophilic granular cells in chromaffin tissue of the adrenal glands, and (6) in the ileum, increased heterophilia in the lamina propria and, only in females, the apoptosis to mitosis ratio in crypt cells of the epithelium. The ducks' outward appearance gave no indication that ingesting large amounts of cadmium for 4½ mo produced deleterious effects, but the physiological consequences were profound. Both sexes had greatly reduced gonadal mass and the males produced no sperm. The higher dietary level greatly hypertrophied the liver, kidneys, and gut only in males. The cadmium-induced changes in organs, particularly in the gonads, kidneys, and adrenal glands, should greatly impair the health and reproductive capacity of these ducks.

ISSN:1528-7394    

DOI:10.1080/00984100050194117

出版商:Informa UK Ltd    

年代:2000

数据来源: Taylor

摘要:

In the present study, the effects of ochratoxin A (OTA) on cytotoxicity, cell differentiation, and other cell functions in the embryonic midbrain cells, which are dopaminergic, were compared to those in the limb bud cells, which are nondopaminergic, to assess the selectivity of OTA central action. Twelve-day rat embryo midbrain and limb bud cells were cultured in Dulbecco's modified Eagle's medium nutrient and Ham's F12 (1:1) mixture containing 10% Nuserum for 96 h in the presence of various concentrations of OTA. OTA significantly reduced the levels of protein, DNA and glutathione, and [3H]thymidine incorporation into DNA in both embryonic midbrain and limb bud cells in a similar concentration-dependent manner. The IC50 values for cytotoxicity measured by neutral red uptake were 1.10 µ M in the midbrain cells and 1.05 µ M in the limb bud cells. The IC50 values of cell differentiation were 1.10 µ M in the midbrain cells and 1.0 µM in the limb bud cells. The addition of exogenous glutathione (32.5 µ M) did not change the OTA-induced fall in protein and DNA levels, or the IC50 values of cytotoxicity and differentiation in the midbrain and limb bud cells. Data show that OTA does not appear to exert a selective toxic dopaminergic cell action and that OTA-induced cytotoxicity and inhibition of cell differentiation were not prevented by exogenous glutathione.

ISSN:1528-7394    

DOI:10.1080/00984100050194126

出版商:Informa UK Ltd    

年代:2000

数据来源: Taylor

摘要:

The objectives of this investigation were to study the effects of hypo- and hyperthyroidism on some factors involved in lung injury under basal conditions (air exposure) and during an inflammatory response induced by inhalation exposure to lipopolysaccharide (LPS; 100 µg/ml; 3 h) in adult rats. Thyroid status was altered by thyroidectomy or thyroxine injections for 15 d. Hyperthyroidism alone caused a greater degree of lung cell damage, an increase in the permeability of the alveolar-capillary barrier, a rise in the total number of phagocytic cells obtained by bronchoalveolar lavage (BAL), and enhanced nitric oxide (NO) release by phagocytic cells relative to that in euthyroid control animals. Hypothyroidism alone was associated with opposite effects. Exposure of animals to LPS produced inflammatory responses, which included significant increases in lung cell damage, permeability of the alveolar-capillary barrier, number of phagocytic cells obtained by BAL, and NO production by the phagocytic cells. In general, hyperthyroidism enhanced the effects of LPS, while hypothyroidism reduced LPS-induced responses. These results suggest that thyroid status alone can affect some of the factors involved in lung injury and also modulate some of the inflammatory effects of LPS. Hyperthyroidism tends to enhance lung injury, while hypothyroidism seems to reduce lung injury.

ISSN:1528-7394    

DOI:10.1080/00984100050194135

出版商:Informa UK Ltd    

年代:2000

数据来源: Taylor