摘要:

AbstractThe ability of tumor promoters to suppress the development of contact hypersensitivity (CHS) was assessed by the mouse ear swelling assay. Application of the complete or second stage tumor promoters phorbol‐12‐myristate‐13‐acetate (PMA, 2 μg), croton oil (1%), benzoyl peroxide (20 mg), mezerein (2 μg), or phorbol‐12‐retinoate‐13‐acetate (PRA, 2 μg) to the abdominal surface of CF‐1 female mice for 1 week (three treatments) prior to the sensitization of the same location with 0.5% 1‐chloro‐2,4‐dinitrobenzene (DNCB) resulted in a 50% suppression (p<0.05) of the CHS response to DNCB. The first stage tumor promoters 4‐O‐Me‐PMA (80 μg), calcium ionophore A23187 (80 μg), hydrogen peroxide (15%) and the non‐promoting analogs phorbol‐12,13‐diacetate (PDA, 20 μg), phorbol (80 μg) or acetone did not suppress the response. The suppression of the development of CHS caused by PMA was dependent on the promoter being applied at the site of induction and was inhibited by application of the phospholipase A2inhibitor dibromoacetophenone (100 μg), the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA, 100 μg), or the antiinflammatory steroid fluocinolone acetonide (2 μg). Application of PMA or mezerein 24 h prior to challenge with DNCB, to the ears of mice previously sensitized with DNCB resulted in a significant enhancement of the ear swelling response by 60% and 110%, respectively, compared with controls. The results demonstrate that tumor promoters suppress the development of CHS, and suggest the possibility that second stage promotion may involve suppression of the de

ISSN:0260-437X    

DOI:10.1002/jat.2550080102

出版商:John Wiley&Sons, Ltd.    

年代:1988

数据来源: WILEY

摘要:

AbstractResults from this study indicate that caffeine at an embryotoxic dose equal to the LD40administered to 3‐day chick embryos produced both ultrastructural and functional abnormalities in embryonic cardiac mitochondria. The principal effects of caffeine on the ultrastructure of embryonic myocardial cells were clearly suggestive of cellular injury and included: (1) a marked disruption of mitochondrial cristae with formation of intramitochondrial myelin‐like figures and (2) intracellular edema. A biochemical analysis of mitochondrial function revealed that caffeine inhibited the capacity of mitochondria to oxidize succinate. However, when pyruvate and malate were employed as substrates for isolated mitochondria, caffeine did not significantly alter mitochondrial function. Interference with embryonic cardiac mitochondrial succinate oxidation and/or fragmentation of mitochondrial membranes are suggested as possible events in the pathogenesis of caffeine‐induced cardiac cell injury which, in turn, may lead to the embryonic death of the

ISSN:0260-437X    

DOI:10.1002/jat.2550080103

出版商:John Wiley&Sons, Ltd.    

年代:1988

数据来源: WILEY

摘要:

AbstractAn epidemiologic investigation was carried out to study the significance of urinary excretion of metallothionein (MT) in people aged 50 years and over living in a cadmium (Cd)‐polluted area in Japan. The urinary level of MT was compared with various parameters (age, urinary α1‐microglobulin (α1‐MG), β2‐microglobulin (β2‐MG), total protein, Cd, copper (Cu), and zinc (Zn), and relative clearances to creatinine of α1‐MG, β2‐MG, phosphate and uric acid). It was found that the urinary excretion of MT is closely associated with Cd and the indices of renal dysfunction listed above. This observation was more remarkable in women than men. When subjects with signs of renal dysfunction were compared as a group to those with normal renal functions, the excreted amount of MT in the former is significantly greater. The results support the notion that the urinary excretion of MT reflects not only Cd exposure levels but also renal dysfunction caused by lo

ISSN:0260-437X    

DOI:10.1002/jat.2550080104

出版商:John Wiley&Sons, Ltd.    

年代:1988

数据来源: WILEY

摘要:

AbstractCytochemical studies were carried out on rat alveolar and peritoneal macrophage cultures following exposure to quartz and corundum dusts. Quartz increased the number of ATPase positive cells and brought about an enhancement in the peroxidase and diffusion of the acid phosphatase activity of the exposed cells. In unexposed cell cultures, acid phosphatase activity was higher in alveolar than in peritoneal macrophages and was dependent upon the duration of incubation. Corundum produced no significant effect on the enzyme activity. Quartz treatment did not alter esterase activity whereas corundum exposed cultures showed a decline. A significant increase in mitochondrial succinic dehydrogenase activity was observed in peritoneal macrophages after quartz treatment. The results demonstrate alteration in the marker enzymes of plasma membranes, mitochondria and lysosomes during phagocytosis of quartz dust as the key event of dust cell interactionin vitro.

ISSN:0260-437X    

DOI:10.1002/jat.2550080105

出版商:John Wiley&Sons, Ltd.    

年代:1988

数据来源: WILEY

摘要:

AbstractThe effect of amrinone on platelet production was differentiated from that of a known bone‐marrow cytotoxic agent (cyclophosphamide) and anti‐platelet serum (APS). The rate of platelet production has been observed over a 4‐day period in the Gunn rat using [75Se]selenomethionine cohort labelling of platelets following administration of either amrinone, 160 mg kg−1day−1, cyclophosphamide, 30 mg kg−1day−1or APS, 0.75 ml. Platelet numbers were reduced by amrinone, cyclophosphamide and APS. The rate of platelet production was increased following APS and suppressed by cyclophosphamide, but the rate of platelet production when expressed as the selenomethionine incorporation in counts per minute (cpm) per 108platelets appeared to be increased in amrinone‐treated animals. When these values are expressed as radioactivity per unit platelet volume the difference between the control and the amrinone‐treated group was reduced but the difference between the control, APS‐ and cyclophosphamide‐treated groups remained unchanged. It is concluded that in the Gunn rat amrinone affects platelet production by producing fe

ISSN:0260-437X    

DOI:10.1002/jat.2550080106

出版商:John Wiley&Sons, Ltd.    

年代:1988

数据来源: WILEY

摘要:

AbstractTwo structurally related acetylenic compounds, 5,7,11‐Dodecatriyn‐1‐ol, (Compound A), and 5,7,11,13‐Octadecatetrayne‐1,18‐Diol (Compound B), were evaluated in a tier I toxicology testing program as part of an ongoing research and development program. This battery of acute tests included acute oral, guinea pig maximization, photosensitization, dermal irritation, Ames and multiple genetic endpoint and a 2 week oral fetotoxicity study. Compound A was found to have an oral LD50of 0.25 ml/kg, be an extreme dermal sensitizer, a mild dermal irritant (PDII of 1.7), and not mutagenic or fetotoxic in the tests employed. Compound B had an oral LD50greater than 4 g/kg, was a moderate dermal sensitizer and mild dermal irritant (PDII of 1.4), was not mutagenic in the Ames test but weakly increased the incidence of SCEs and gene mutations in Chinese Hamster Ovary cells, and was not fetotoxic. Neither compound was found to be a photosensitizer, but during the course of the photosensitization study Compound A was found to cause neuromuscular signs (including hind limb paralysis) and a bilaterial necrosis of the medulla oblongata in female guinea pigs. A similar lesion was found in female rats receiving a single oral dose of 0.25 ml/kg and in nonpregnant females dosed daily for two weeks at 0.03 ml/kg. Compound B was not found to produce any of these neurolo

ISSN:0260-437X    

DOI:10.1002/jat.2550080107

出版商:John Wiley&Sons, Ltd.    

年代:1988

数据来源: WILEY

摘要:

AbstractThe mechanism of Tris‐BP or Bis‐BP (a metabolite of Tris‐BP) induced nephrotoxicity was investigated by determining urinary excretion of enzymes and selected metabolites. Rats received single oral doses of 0, 71.7, 143.4 and 286.8 μmol/kg tris (2,3‐dibromopropyl) phosphate (Tris‐BP) or bis (2,3‐dibromopropyl) phosphate (Bis‐BP). Urine was collected over a 24 h period and subjected to biochemical examinations. Comparative studies on Tris‐BP‐ and Bis‐BP‐induced nephrotoxicities were carried out for abnormal patterns of urinary excretion. The urinary excretion of glucose was higher in Bis‐BP than Tris‐BP at a dose of 143.4 μmol/kg, but this pattern reversed at a dose of 286.8 μmol/kg. Peak lactate excretion occurred later than peak glucose excretion with 143.4 and 286.8 μmol/kg Tris BP and 143.4 μmol/kg Bis‐BP. Bis‐BP 286.8 μmol/kg caused a transient urinary elevation of lactate on Day 2. Uric acid was excreted at higher levels for Bis‐BP than Tris‐BP on day 2 of urine collection. Activities of urinary enzymes including alkaline phosphatase, aspartate aminotransferase and γ‐glutamyltransferase, were different on the first day of post‐treatment for Tris‐BP and Bis‐BP. Leucine aminopeptidase and lactate dehydrogenase levels differed on the second day. Activities of the former enzymes on the day 2 urine suggested a transformation of Tris‐BP to Bis‐BP. Urinary patterns of lactate dehydrogenase isoenzymes (LDH‐1‐LDH‐5) were different between Tris‐BP and Bis‐BP when rats were treated with the dose of 286.8 μmol/kg: Tris‐BP caused a higher excretion of LDH‐4 and LDH‐5 in urine on day 1 and all five isoenzymes into the day 2 urine. Bis‐BP caused slightly higher excretion of LDH‐5 and LDH‐4 into the day 1 and 3 urine, respectively. Bis‐BP but not Tris‐BP caused abnormally urinary excretion of sodium ion. Histopathologically, the nephrotoxic effect of Tris‐BP appeared one day later

ISSN:0260-437X    

DOI:10.1002/jat.2550080108

出版商:John Wiley&Sons, Ltd.    

年代:1988

数据来源: WILEY

摘要:

AbstractThe effects of neurotoxic solvents, i.e. 2,5‐hexanedione (2,5‐HD), 2,5‐hexanediol (2,5‐HDiol) and the non‐neurotoxic solvent, 2,4‐hexanedione (2,4‐HD) (500 mg/kg body wt./day, i.p.), have been studied on the lipid composition of brain and sciatic nerves in weanling rats. Five‐day‐old rats were administered a solvent daily for 21 days. Clinical signs of peripheral neuropathy appeared in 2,5‐HD and 2,5‐HDiol treated groups. Absolute weights of brain, spleen, thymus significantly decreased with 2,5‐HD. Cholesterol content in whole brain homogenates and myelin was significantly reduced with 2,5‐HD and 2,5‐HDiol treatment. There was also a significant reduction in ubiquinone content of brain with 2,5‐HD and 2,5‐HDiol treatment. On exposure to neurotoxic chemicals to weanling rats, significant alteration in lipid profile was observed in the brain, which may be one of the key factors i

ISSN:0260-437X    

DOI:10.1002/jat.2550080109

出版商:John Wiley&Sons, Ltd.    

年代:1988

数据来源: WILEY

摘要:

AbstractThe sensitivity of different parameters for the determination of lung injury caused by nitrogen dioxide (NO2) was investigated. Male rats were exposed to concentrations of 0, 4, 10 or 25 ppm NO2for 6 h/day, for 7, 14 or 21 days. Histopathology of the nasal cavity, larynx, trachea and lungs was compared with the changes in macrophage function and morphology. In addition several biochemical parameters were determined in lung lavages. Cytotoxic effects were investigated in primary cultures of rat and bovine alveolar macrophages, exposed to the same NO2‐levels as in thein vivoexposure. Treatment‐related histopathological changes were observed in the lungs. No differences between exposed and control animals were observed in the nasal cavity, larynx or trachea. The morphology of the lavaged alveolar macrophages was changed at all exposure concentrations on day 7, 14 and 21. An increase in the number of macrophages was found after exposure to 10 and 25 ppm NO2on days 7, 14 and 21. The phagocytic capacity was diminished after 14 and 21 days exposure to 25 ppm and at both times exposure to 10 and 25 ppm increased the level of gamma‐glutamyl transferase (GGT) in lavage fluids. Morphology of the macrophages and levels of GGT were found to be sensitive parameters of nitrogen dioxide toxicity.In vitroexposure of rat and bovine alveolar macrophages to comparable NO2‐concentrations induced effects on phagocytosis similar to those observed for macrophages from expos

ISSN:0260-437X    

DOI:10.1002/jat.2550080110

出版商:John Wiley&Sons, Ltd.    

年代:1988

数据来源: WILEY

摘要:

AbstractGuinea‐pigs were exposed to 400 ppm or 5500 ppm of isoprophyl alcohol (IPA) for 24 successive hours, and they were killed immediately after the exposure period. The ciliary activities of the nose and trachea were examined. In addition, the epithelium of the nose and trachea was observed by scanning and transmission electron microscopy.The present study showed that exposure to 400 or 5500 ppm of IPA vapor caused deterioration of the ciliary activity and also some pathological changes. Although our study revealed that exposure to 400 ppm of IPA vapor can affect the mucosa of the nose and trachea, the ciliary activity of the 400‐ppm exposure group was not too poor and morphological changes were rather mild. Recovery from such degeneration might be rapid. Therefore, our study supports the justification of the allowable IPA level recommended by AC

ISSN:0260-437X    

DOI:10.1002/jat.2550080111

出版商:John Wiley&Sons, Ltd.    

年代:1988

数据来源: WILEY