摘要:

AbstractWide attention has been given to hyperthermia as a new measure for cancer treatment. Clinical trials of hyperthermia, as they possess antitumour activity on some occasions. When cells were incubated with oleic we examine if fatty acids exert a synergistic effect on Ehrlich ascites tumour cells when combined with hyperthermia, as they pssess antitumour activity on some occasions. When cells were incubated with oleic acid and linoleic acid (unsaturated fatty acids) at 37°C, the DNA synthesis of cells was significantly inhibited. Palmitic and stearic acids, which are saturated fatty acids, did not suppress DNA synthesis. Hyperthermic treatment without the presence of fatty acids at 42°C for 1 h decreased DNA synthesis to 62% of the control level of 37°C. The combination of an unsaturated fatty acid and hyperthermia synergistically suppressed DNA synthesis. When the cells were incubated in serum‐free medium containing 0.1 % albumin, unsaturated fatty acids were more effective in inhibiting DNA synthesis. However, saturated fatty acids had little or no effect on DNA synthesis in control or hyperthermia‐treated cells. These results indicate that unsaturated fatty acids are useful for enhancing the inhibitory effect of hyperthermia on DNA synthesis, which may increase thein vitroantitumour effects of hypert

ISSN:0260-437X    

DOI:10.1002/jat.2550090102

出版商:John Wiley&Sons, Ltd.    

年代:1989

数据来源: WILEY

摘要:

AbstractOrganophosphorus (OP) pesticides are considered to be environmental contaminants, and chronic exposure to low levels through the diet may affect drug action. To study this possible interaction, ethyl parathion was administered by intubation to female rats for 35 consecutive days at a dose of 0.05 or 0.2 mg/kg of body weight per day. At 7, 21 and 35 days after parathion was initiated, rats were administered a single dose of 20 mg/kg sodium salicylate intraperitoneally. Total salicylates, salicyclic acid (SA), salicyluric acid (SU) and gentisic acid (GA) were determined in urine. At 7 days, parathion treatment slowed the excretion of total salicylates. This effect was more evident at longer treatment times. Total excretion of SA was increased at the expense of GA at 7 days. However, this effect was reversed at 21 and 35 days. Excretion of SU was drastically diminished after 21 days of treatment with parathion. The results suggest that subchronic oral administration of parathion to female rats changes the excretion kinetics of sodium salicylate through combined effects on renal excretion mechanisms and biotransformation processes. Thus, exposure to low concentrations of environmental contaminants may produce important changes in drug action.

ISSN:0260-437X    

DOI:10.1002/jat.2550090103

出版商:John Wiley&Sons, Ltd.    

年代:1989

数据来源: WILEY

摘要:

AbstractHalothane‐induced hepatic microsomal lipid peroxidation in guinea pigs and rats was examined with respect to the mixed function oxidase system, anaerobic dehalogenation activity of halothane, and the antioxidant system. The levels of cytochrome P‐450 and NADPH‐cytochrome P‐450 reductase were significantly higher in guinea pigs than in rats. There was no difference between the two animals in anaerobic dehalogenation activity of halothane per cytochrome P‐450 in microsomes. Microsomal α‐tocopherol was significantly lower in guinea pigs than in rats, and was increased by multiple exposure to halothane in guinea pigs but remained lower than in rats. Microsomal α‐tocopherol was decreased in rats by multiple exposure. The concentration of reduced glutathione and ascorbic acid was decreased significantly by multiple exposure to halothane in guinea pigs but not in rats. These results suggest that the higher level of halothane‐induced hepatic microsomal lipid peroxidation in guinea pigs is due to the large production of radical metabolites resulting from the large amounts of cytochrome P‐450, the high activity of NADPH‐cytochrome P‐450 reductase, and the low concentration of

ISSN:0260-437X    

DOI:10.1002/jat.2550090104

出版商:John Wiley&Sons, Ltd.    

年代:1989

数据来源: WILEY

摘要:

AbstractSubacute toxicity of trichloroethylene (TCE) was evaluated in male and female B6C3F1 mice using corn oil or aqueous gavage vehicles. Mice received oral doses of TCE five times a week for 4 weeks at 600, 1200 and 2400 mg/kg/day for males and 450, 900 and 1800 mg/kg/day for females. Vehicle control mice were dosed with either corn oil or a 20% aqueous solution of Emulphor. A dose‐related increase n lethality occurred in male and female mice receiving TCE in Emulphor but not corn oil during the first week of treatment. Lethality was consistent with central nervous system depressant effects of TCE. After 4 weeks of exposure, body weights were not altered by TCE but liver/body weight ratios were uniformly increased by TCE administered in either vehicle in both sexes. Only male mice treated with TCE in corn oil, however, sustained elevations in serum enzyme levels, accompanied by liver histopathology. TCE in corn oil produced inflammation‐associated focal necrosis in 30–40% of the male mice, with increasing severity from low to high dose. Lipid accumulation, as indicated by Oil‐Red O staining, was most prevalent in male mice treated with TCE in corn oil but also occurred to a lesser degree in animals receiving either gavage vehicle alone. This study indicates that the type of oral gavage vehicle is an important factor in determining the nature of TCE t

ISSN:0260-437X    

DOI:10.1002/jat.2550090105

出版商:John Wiley&Sons, Ltd.    

年代:1989

数据来源: WILEY

摘要:

AbstractThe potential carcinogenic effect of inhaled automobile exhaust emissions was examined in rodents. Both rats and hamsters were exposed to the emissions from (1) a gasoline engine, (2) a gasoline engine fitted with a three‐way catalytic converter, (3) a diesel engine and (4) a diesel engine with particle filtration. Exposures were for 16 hours per day, 5 days per week, for 2 years. All hamsters were sacrificed at the end of the 2 year exposure period, whereas the rats surviving after 2 years of exposure were maintained for a further 6 month observation period without additional exposure to emissions. Some of the hamsters in each treatment group were pretreated with diethylnitrosamine to induce respiratory tract tumours.No statistically significant changes were seen in the incidence of respiratory tract tumours in emission‐exposed hamsters compared to controls. This lack of a treatment‐related effect was seen in both the nitrosamine pretreated and the non‐pretreated hamsters.There was no increase in the incidence of lung tumours in rats exposed to filtered diesel exhaust or to the exhaust from the gasoline or gasoline‐catalyst engines.There was a statistically significant increase in the incidence of lung tumours in rats exposed to diesel engine emissions compared to controls. A clear dose response was evident in both males and females, although the incidence of lung tumours was markedly higher in females (96% in rats surviving beyond 2 years) than in males (44% in rats surviving beyond 2 years). An increased incidence of lung tumours was observed only in rats exposed to mean concentrations of diesel soot particles of either 2200 or 6600 μ/m3. No increase was observed at 700 μ/m3. In comparison, the projected mean concentration of diesel soot particles in major US cities with 20% of light‐duty vehicles diesel‐powered has been estimated

ISSN:0260-437X    

DOI:10.1002/jat.2550090106

出版商:John Wiley&Sons, Ltd.    

年代:1989

数据来源: WILEY

摘要:

AbstractMarmosets were given either a hepatotoxin, carbon tetrachloride, orally or an i.m. injection of a mytoxin, chlorpromazine. Although muscle damage alone caused small increases in the plasma levels of lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase and isocitrate dehydrogenase (ICDH), only the isoenzyme analysis of ICDH can differentiate definitely between liver and muscle damage. Only very severe muscle damage can increase the plasma concentration of this enzyme but, in this case, the elevation of plasma creatinine kinase levels helps differentiation. It is recommended that the elevation of ICDH is the most specific indicator of hepatic damage in the marmoset.

ISSN:0260-437X    

DOI:10.1002/jat.2550090107

出版商:John Wiley&Sons, Ltd.    

年代:1989

数据来源: WILEY

摘要:

AbstractTo study the significance of damage to the nasal mucosa for the induction of nasal tumours by formaldehyde in rats, a long‐term inhalation study was conducted in which male rats with severely damaged or undamaged nose were exposed 6 h/day for 5 days/week to 0, 0.1, 1.0 or 10 ppm formaldehyde vapour for 28 months, or for 3 months followed by a 25‐month observation period. The damage to the nasal mucosa was induced by bilateral intranasal electrocoagulation. The total number of rats used was 720, 480 with damaged and 240 with intact nose.Compound‐related degenerative, inflammatory and hyperplastic changes of the nasal respiratory and olfactory mucosa were invariably observed when rats with intact nose were exposed to 10 ppm but not when exposed to 1.0 or 0.1 ppm formaldehyde. Nasal electrocoagulation increased the incidences of formaldehydeinduced rhinitis, hyper‐ and metaplasia of the respiratory epithelium, and degeneration and hyper‐ and metaplasia of the olfactory epithelium. In addition, exposure to 10 ppm formaldehyde for 28 months produced nasal squamous cell carcinomas in rats with damaged nose (15/58) but not in rats with intact nose. Three months of exposure to 10 ppm formaldehyde or exposure to 0.1 or 1.0 ppm formaldehyde for 28 months had no such effect. It was concluded that severe damage to the nasal mucosa may contribute to the induction of nasal tumours by for

ISSN:0260-437X    

DOI:10.1002/jat.2550090108

出版商:John Wiley&Sons, Ltd.    

年代:1989

数据来源: WILEY

摘要:

AbstractThe susceptibility of the cardiovascular system to exposure to a high‐boiling coal liquid (heavy distillate, HD) was studied in the rat using an isoproterenol (ISO) myocardial infarction model. Male Fischer rats were exposed to HD by inhalation (0.7 mg/l), 6 h/day, 5 days/week, for 6 weeks. After a 10‐day recovery period, sham‐exposed and HD‐exposed rats were injected subcutaneously with 0, 20, 40 or 60 mg ISO/kg body weight. Blood pressure, heart rate, electrocardiogram and99mTc uptake by the heart were measured 1 day later. A dose‐related increase was observed in the uptake of99mTc by the hearts of both sham‐exposed and HD‐exposed animals after ISO injection; however, uptake by the sham‐exposed group was significantly greater than that of exposed groups. The most striking observation was a 20% elevation in arterial blood pressure of HD‐exposed rats over that of sham‐exposed animals when no ISO was injected. These results suggest that the cardiovascular system could be detrimentally affected by exposure to coal‐derived complex mixtures and, possibly, to other com

ISSN:0260-437X    

DOI:10.1002/jat.2550090109

出版商:John Wiley&Sons, Ltd.    

年代:1989

数据来源: WILEY

摘要:

AbstractThe interaction of 2[14C]methyl‐2,3[14C]acrylonitrile (MeAN) with the components of blood and its disposition in male Sprague‐Dawley rats has been investigated. Following an oral administration of 100 mg/kg (0.5LD50, 8 μCi/kg), the rats excreted 43% of the [14C] in the urine, 15% in the feces and 2.5% in the expired air as14CO2in 5 days. Hydrogen cyanide (H14CN) was not detectable. The red blood cells retained significant amounts of radioactivity for more than five days after administration, whereas the [14C]‐activity in plasma declined sharply. More than 50% of the radioactivity in erythrocytes was detected as covalently bound to cytoplasmic (hemoglobin) and membrane proteins. A small amount of radioactivity was also found in the heme fraction. About 13% of the total dose administered was recovered as thiocyanate in the plasma and the urine. These results suggest that the toxicity of MeAN may be attributable to the whole molecule and not entirely to thein vivoliberation of c

ISSN:0260-437X    

DOI:10.1002/jat.2550090110

出版商:John Wiley&Sons, Ltd.    

年代:1989

数据来源: WILEY

摘要:

AbstractThe acute toxicity of three materials derived from Athabasca Oil Sands—(1) bitumen plus naphtha, (2) untreated naphtha (0–250°C) and (3) synthetic crude oil (0–500°C)— was assessed in a battery of tests. In acute oral studies, all three test materials exhibited a low order of toxicity (LD50>5.0 g kg−1). The acute dermalLD50was also low (>3 g kg−1) for each test material. All three materials were judged to be ‘slight’ ocular irritants. Acute inhalation studies (6‐h exposures at the maximum attainable concentrations) produced varied responses. Bitumen plus naphtha administered at a concentration of 1.46 mg l−1did not cause mortality in exposed rats or mice. Lung discoloration was the only necropsy finding of note. Untreated naphtha administered at a concentration of 10.6 mg l−1was lethal to essentially all of the mice;but only two rats died. Necropsy findings included elevated weights in the liver and kidneys of the exposed mice, elevated lung weights in male rats and elevated liver weights in female rats. Synthetic crude oil administered at a concentration of (4 mg l−1) was lethal to 5/10 mice, but none of the rats (0/10) died. Severe hair loss was noted in the surviving mice, and slight alopecia was also observed in rats. Both species exhibited elevated liver weight, and elevated lung weight

ISSN:0260-437X    

DOI:10.1002/jat.2550090111

出版商:John Wiley&Sons, Ltd.    

年代:1989

数据来源: WILEY