摘要:

AbstractOur previous studies indicated the involvement of some unidentified mechanisms, apart from the bioactivation phenomenon, in chlordecone (CD)‐potentiated CCl4hepatotoxicity and lethality. Recent studies revealed that hepatocellular regeneration is suppressed in CD + CCl4toxicity. The present work is a continuation of our earlier work employing a partial hepatectomy model for stimulating hepatocellular division, in normal (N) or CD‐treated (10 ppm for 15 days) rats. Male Sprague‐Dawley rats maintained on an appropriate dietary protocol and undergoing sham (SH) or partial hepatectomies (PH) were employed. Hepatocellular regeneration was assessed by measuring the percentage mitotic figures and by autoradiography of liver sections from rats given3H‐thymidinein vivo. Hepatotoxicity was assessed by examining liver sections for necrotic cells, swollen cells and cells having lipid droplets. CCl4(100 μl kg−1)‐induced histopathological alterations in CD‐pretreated rats were significantly decreased in rats 2 days post‐PH (PH2) as compared to SH rats or rats 7 days post‐PH (PH7), indicating that amplification of CCl4toxicity is significantly reduced when there is a greater regenerative activity. The percentage of mitoses as well as the percentage of labelled cells were significantly elevated at 2–6 h after CCl4administration in N rats but remained suppressed in CD rats. In CD‐pretreated PH2rats where the percentage of mitoses and the percentage of labelled cells were many‐fold greater when compared to SH or PH7rats, a portion of the stimulated hepatocellular division decreased significantly at 2–6 h after CCl4administration, but remained significantly greater when compared to basal level of regeneration. These results support our concept that suppression of hepatocellular regeneration is one of the events responsible, besides the bioactivation phenomenon, for the CD‐po

ISSN:0260-437X    

DOI:10.1002/jat.2550090602

出版商:John Wiley&Sons, Ltd.    

年代:1989

数据来源: WILEY

摘要:

AbstractThe potential teratogenic hazard of five compounds was evaluated using the Frog Embryo Teratogenesis Assay—Xenopus(FETAX) and a metabolic activation system. Embryos of the South African clawed frog,Xenopus laevis, were exposed to (i) three compounds suspected to be proteratogenic in mammalian test systems—[2‐acetylaminofluorene (2‐AAF), rifampicin (RA) and benzo[a]pyrene (BP)]for 96 h; (ii) one compound unaffected by mixed‐functional oxidase (MFO) metabolism—ZnSO4; (iii) one compound thought to be inactivated by cytochrome P‐450—cytochalasin D (CD). Two separate static renewal tests were conducted with and without the presence of an exogenous metabolic activation system (MAS). The metabolic activation system consisted of Aroclor 1254‐induced rat liver microsomes. The teratogenic potential of each compound and the effects of metabolic activation were based on teratogenic indices [TI=96 hLC50/96 hEC50(malformation)], types and severity of malformation, and effects on embryo growth. Metabolic activation increased the potential teratogenic hazard of 2‐AAF, RA and BP byTIfactors of 1.3, 2.8 and 6.8, respectively. The teratogenic potential of ZnSO4was virtually unaffected by the MAS. The MAS significantly reduced the teratogenic potential of CD by aTIfactor of 2.7. These results demonstrate the utility and importance of a MAS forin vitrodevelopmental toxicity screens such as FETAX. Consistent use of a MAS with FETAX should reduce the number of potential false‐positive and false

ISSN:0260-437X    

DOI:10.1002/jat.2550090603

出版商:John Wiley&Sons, Ltd.    

年代:1989

数据来源: WILEY

摘要:

AbstractThe aim of this work was to evaluate the mutagenic activity of airborne particulate matter in the rubber industry. Air was sucked through Whatman glass‐fibre filters with Staplex pumps and adsorbed substances and fume particles were extracted with acetone or toluene for 2 h in a ultrasonic cleaner. After separation of the insoluble solid phase by filtration, solvent was evaporated at a temperature of 70°C in an argon atmosphere. The residue was stored at −20°C. Mutagenicity was determined by theSalmonellaplate incorporation assay with the tester strain TA98 and activity is related either to the weight of aerosol (rev mg−1) or to the volume of atmospheric sample (rev m−3). The fumes emitted from the tyre tread line, calender feeding, and tyre vulcanizing processes, showed the highest mutagenic activity (55–211 rev mg−1, + S9). At these and at other workplaces (extruder mill, carbon black station, mixer loading), mutagenic activity related to the volume of air was in the range of 22–158 rev m−3, + S9. The results indicate the need to reduce and monitor mutagenic contamination in order to increase the safety of work in th

ISSN:0260-437X    

DOI:10.1002/jat.2550090604

出版商:John Wiley&Sons, Ltd.    

年代:1989

数据来源: WILEY

摘要:

AbstractMale Wistar rats were given 0.5 and 2% lead acetate in drinking water for 2 months, 1% lead acetate for 3 months and sodium acetate equimolar to 2% lead acetate for 3 months. Glucose, total proteins, lactate dehydrogenase (LDH), lysozyme and β2‐microglobulin (β2‐m) were measured in 24‐h urine every month. Kidney weight and histology were also examined.At the three doses, lead exposure produced a significant elevation of the kidney weight. No significant change in urinary parameters was observed in rats given 0.5% lead acetate. Exposure to 1% lead acetate increased the urinary excretion of β2‐m only.At the 2% lead acetate dose the elevation of β2‐m excretion was accompanied by an increased urinary output of glucose, total proteins, lysozyme and LDH. Observations of the kidneys by light microscopy were in agreement with these biochemical findings. The nephrotoxic effect of acetate was excluded by the lack of biochemical or histological effects of sodium acetate on the kidney. It is concluded that a proximal tubular dysfunction is induced in rats chronically exposed to high

ISSN:0260-437X    

DOI:10.1002/jat.2550090605

出版商:John Wiley&Sons, Ltd.    

年代:1989

数据来源: WILEY

摘要:

AbstractThe effects of ethyl parathion on the activities of various renal enzymes were studied in the offspring from dams treated with this insecticide during pregnancy. The enzymes tested were the (Na+‐K+)‐ and the Mg2+‐dependent ATPases, the glutathioneS‐transferases and carboxylesterases. The postnatal effects of parathion on kidney ATPases from undernourished rats were also assessed. The organophosphate was administeredper osto pregnant rats at a dose of 1 mg kg−1body weight per day throughout gestation, and suspended after delivery. The offspring were divided in groups of normally‐fed and undernourished rats. In the undernourished group, food restriction produced a decrease of 43% in body weight as compared to the normally‐fed group. Offspring were sacrificed 6 weeks after birth and the enzymatic activities were determined in kidney homogenates. We found a decrease in the enzymatic activity of total ATPases, at the expense of the Mg2+‐dependent ATPase. However, the activities of the (Na+‐K+)‐dependent ATPase, the glutathioneS‐transferases and the carboxylesterases did not show significant changes. On the other hand, undernutrition did not potentiate the effects of parathion on the ATPases. Thus, this organophosphate administered during pregnancy produced a selective inhibition on the renal Mg2+‐dependent ATPase from offspring, which was not potentiated by our

ISSN:0260-437X    

DOI:10.1002/jat.2550090606

出版商:John Wiley&Sons, Ltd.    

年代:1989

数据来源: WILEY

摘要:

AbstractFunctional, biochemical and histological parameters of hepatotoxicity were assessed in male Sprague‐Dawley rats receiving amiodarone (Am) short‐term by gavage (5, 50, 150 and 500 mg Am kg−1day−1, 10 days) or dietary exposure (50 ppm, 1500 ppm, 4‐week duration), or by long‐term dietary exposure (50 ppm, 8‐month duration). Serum enzyme (ALT, AST, ICD) levels and histopathological examination indicated no observable evidence of toxicity among rats of any of the treatment groups. Reduced food intake and reduction in weight gain was observed for rats exposed short‐term to 1500 ppm dietary Am. Assessment of hepatobiliary function in treated rats indicated that short‐term and long‐term dietary exposure to Am resulted in a compromised excretion of readily excretable phenolphthalein glucuronide (PG), although inanition may account for this effect in the 1500 ppm group. Rats receiving Am by gavage exhibited a reduction in biliary excretion of PG, which was not dose‐dependent. Distribution of Am and its major metabolite, desethylamiodarone, was similar to previous reports wherein both compounds accumulated in adipose, lung and liver tissue. These data suggest that minor alterations of hepatobiliary function occur in the absence of histological alterations and may preceed biochemical changes, as a

ISSN:0260-437X    

DOI:10.1002/jat.2550090607

出版商:John Wiley&Sons, Ltd.    

年代:1989

数据来源: WILEY

摘要:

AbstractThe teratogenic potential of dibenzthiazyl disulphide (MBTS) was studied in Wistar rats. Pregnant rats were given MBTS at a dosage of 0, 0.04, 0.2 or 1% in the diet from day 0 to day 20 of pregnancy. Daily intakes of MBTS were 26 mg kg−1for the 0.04% group, 127 mg kg−1for the 0.2% group and 596 mg kg−1for the 1% group. Maternal body weight gain during day 0 to day 14 of pregnancy in the 1% group was significantly lowered, but no significant changes induced by MBTS were observed in any other maternal parameters, such as food consumption and clinical sign of toxicity. There were no significant compound‐related effects on the incidences of pre‐ and postimplantation losses and the number, sex ratio and body weight of live fetuses. Morphological examinations of the fetuses revealed no evidence of teratogenesis. In the postnatal development of the offspring from the dams given MBTS, a high survival rate and good growth of the offspring were seen. It could be concluded that MBTS possesses no adverse effects on the pre‐ and postnatal development of the offspring in rats at the doses employed in the pr

ISSN:0260-437X    

DOI:10.1002/jat.2550090608

出版商:John Wiley&Sons, Ltd.    

年代:1989

数据来源: WILEY

摘要:

AbstractKinetic parameters of aldolases in muscle, gill, liver and brain tissues of the teleostTilapia mossambicawere studied at sublethal concentrations with methyl parathion (MP). The pH activity profiles were optimal at pH 7.0 and 9.0 in gill, liver and brain tissues, whereas only a single peak at pH 7.0 was observed in muscle tissue of both control and MP‐exposed fish. The pH 7.0‐specific peak was confirmed as aldolase A and the pH 9.0‐specific peak represents the tissue‐specific aldolases: aldolase B in liver, aldolase C in brain and aldolase B‐C in gill. It is further confirmed with the inhibitor sensitivity of aldolases at two peaks with 6 × 10−3M ATP or AMP. The pH‐based substrate‐dependent kinetics of aldolases showed a variable trend. The tissue‐specific activity of pH 7.0‐specific aldolases showed low Kmvalues for gill followed by muscle, liver and brain tissues, suggestive of its high enzyme‐substrate affinity. During MP exposure, the Vmaxvalues of pH 7.0‐specific aldolases in muscle, gill and brain were unchanged compared to controls, but Kmvalues were decreased. The pH 9.0‐specific aldolases of gill and liver from MP‐exposed fish showed decreased Kmvalues with a slight increase in Vmaxvalues. Effectors such as lysine, arginine and Ca2+inhibited, while histidine, cysteine, aspartic acid and α‐ketoglutaric acid elevated the activity levels of aldolases. It was concluded that the considerable enhancement in the catalytic efficiency of both the pH 7.0‐ and ph 9.0‐specific aldolases during MP toxicity could be due to a change in the configuration of aldolases or due to a chan

ISSN:0260-437X    

DOI:10.1002/jat.2550090609

出版商:John Wiley&Sons, Ltd.    

年代:1989

数据来源: WILEY

摘要:

AbstractThe toxic effects of 2,4‐dichlorophenol on two strains ofEscherichia coliharbouring plasmids with β‐lactamase activity were studied. The toxicant had a significant effect on growth at concentrations of 12 μg ml−1for the JA 221 (pBR322) strain, as well as at 24 μg ml−1for the J5‐3 (RP4) strain. β‐Lactamase production was affected at concentrations of 96 μg ml−1in both strains. However, β‐lactamase production does not seem to constitute a reliable toxicity test in view of its variability and relat

ISSN:0260-437X    

DOI:10.1002/jat.2550090610

出版商:John Wiley&Sons, Ltd.    

年代:1989

数据来源: WILEY

ISSN:0260-437X    

DOI:10.1002/jat.2550090611

出版商:John Wiley&Sons, Ltd.    

年代:1989

数据来源: WILEY