摘要:

The reproductive performance of the wives of 300 men working in the pharmaceutical factory and exposed to sulfonamides was evaluated. The percentage of abortions, stillbirths, premature births, and live births among the wives of these workers and the frequency of congenital malformations in the offspring were recorded. The reproductive performance of 360 men and their wives who were not exposed to toxic chemicals, drugs, radiations, and so forth and who belonged to the same socioeconomic group served as the control population. There was a significant increase in the percentage of abortions and decrease in live births in the sulfonamide-exposed population when compared to controls.

ISSN:0098-4108    

DOI:10.1080/009841096161816

出版商:Informa UK Ltd    

年代:1996

数据来源: Taylor

摘要:

The clastogenic effects of several new quinolones (ciprofloxacin, enoxacin, levofloxacin, nalidixic acid, ofloxacin, pipemidic acid, and N1-cyclopropyl quinolones for drug candidate) were studied cytogenetically using Chinese ham ster lung cells (CHL) and the mouse micronucleus test. Some N1-cyclopropyl quinolones strongly induced chromosomal aberration on CHL cells, and some, but not all, were also capable of inducing micronuclei in mouse bone marrow cells. Levofloxacin showed weak clastogenicity in CHL cells but did not induce either micronuclei in mouse bone marrow or unscheduled DNA synthesis (UDS) in rat hepatocytes when administered to intact live animals. The lack of concordance between in vitro and in vivo assays could reflect the differences in the tissue levels of the drugs and the in vitro conditions.

ISSN:0098-4108    

DOI:10.1080/009841096161825

出版商:Informa UK Ltd    

年代:1996

数据来源: Taylor

摘要:

The effect of diesel exhaust particles (DEP) on the activity of catalase, an intracellular antioxidant, was investigated because H2O2 is a cytotoxic oxidant, and catalase released from alveolar cells is an important antioxidant in the epithelial lining fluid in the lung. DEP inhibited the activity of bovine liver catalase dose-dependently, to 25-30% of its original value. The inhibition of catalase by DEP was observed only in the presence of anions such as Cl-, Br-, or thiocyanate. Other anions, such as CH3COO- or SO-4, and cations such as K+, Na+, Mg2+, or Fe2+, did not affect the activity of catalase, even in the presence of DEP extract. Catalase from guinea pig alveolar cells and catalase from red blood cells were also inhibited by DEP extracts, as was catalase from bovine liver. These results suggest that DEP taken up in the lung and located on alveolar spaces might cause cell injury by inhibiting the activity of catalase in epithelial lining fluid, enhancing the toxicity of H2O2 generated from cells in addition to that of O2- generated by the chemical reaction of DEP with oxygen.

ISSN:0098-4108    

DOI:10.1080/009841096161834

出版商:Informa UK Ltd    

年代:1996

数据来源: Taylor

摘要:

m-Xylene is a commonly used industrial solvent that has been shown to alter mixed-function oxidase (MFO) activity, in an organ-and isozyme-specific pattern, following intraperitoneal adm inistration of the solvent. The purpose of this work was to determine whether similar alterations occurred in cytochromes P-450 (CYP) following m-xylene inhalation, the primary route of occupational exposure. A single 6-h exposure to m-xylene resulted in the inhibition of aryl hydrocarbon hydroxylase (AHH) activity in the lung while the activity of AHH was unchanged in the liver. CYP 2B1 activity, which is responsible for the metabolism of benzo\[a]pyrene (BaP) to relatively nontoxic metabolites, was decreased in lung but not in liver. The activity of CYP 1A1, responsible for the metabolism of BaP to reactive/toxic products, was not altered in lung or liver. The CYP 2B1/1A1 ratio is an indirect indicator of the pattern of BaP toxication/detoxication. This ratio was decreased in lung, suggesting that BaP metabolism is shifted toward toxication. CYP 1A2 and CYP 4B1 activity was decreased in the lung while remaining unchanged in the liver. CYP 2E1 activity was also inhibited in lung while its activity was increased in the liver. This organ-specific inhibition of pulmonary cytochromes P-450 may be due to the lower MFO activity in the lung compared to liver. Alteration of the cytochromes P450 by m-xylene could result in a change in the metabolic profiles of xenobiotics in coexposure or subsequent exposure scenarios in increased or decreased toxicity in an organ-specific fashion.

ISSN:0098-4108    

DOI:10.1080/009841096161843

出版商:Informa UK Ltd    

年代:1996

数据来源: Taylor

摘要:

The mechanism of arsine (AsH3) induced hemolysis was studied in vitro using isolated red blood cells (RBCs) from the rat or dog. AsH3-induced hemolysis of dog red blood cells was completely blocked by carbon monoxide (CO) preincubation and was reduced by pure oxygen (O2) compared to incubations in air. Since CO and O2 bind to heme and also reduce hemolysis, these results suggested a reaction between AsH3 and hemoglobin in the hemeligand binding pocket or with the heme iron. Further, sodium nitrite induction of methemoglobin (metHb) to 85% and 34% of total Hb in otherwise intact RBCs resulted in 56% and 16% decreases in hemolysis, respectively, after incubation for 4 h. This provided additional evidence for the involvement of hemoglobin in the AsH3-induced hemolysis mechanism. Reactions between AsH3 and hemoglobin were studied in solutions of purified dog hemoglobin. Spectrophotometric studies of the reaction of AsH3 with various purified hemoglobin species revealed that AsH3 reacted with HbO to produce metHb and, eventually, degraded Hb characterized by gross precipitation of the protein. AsH3 did not alter the spectrum of deoxyHb and did not cause degradation of metHb in oxygen, but bound to and reduced metHb in the absence of oxygen. These data indicate that a reaction of AsH3 with oxygenated hemoglobin, HbO2, may lead to hemolysis, but there are reactions between AsH3 and metHb that may not be directly involved in the hemolytic process.

ISSN:0098-4108    

DOI:10.1080/009841096161852

出版商:Informa UK Ltd    

年代:1996

数据来源: Taylor

摘要:

The present studies indicate pronounced species-, sex-, and strain-related differences in the acute nephrotoxicity of hydroquinone (HQ) when administered by gavage to male and female Sprague-Dawley (SD) rats, Fischer 344 (F344) rats, and B6C3F1 mice. Following a single dose of 400 m g/kg, male and female F344 rats displayed pronounced enzymuria and glucosuria. In female F344 rats, urinary alkaline phosphatase and glucose were the most sensitive indicators of renal toxicity, reaching levels of, respectively, 157 times and 137 times control values within 24 h of dosing. HQ treatment of male F344 rats also resulted in significant enzymuria, although it was less marked than that seen in female F344 rats. Significant numbers of epithelial cells were also present in the urine from F344 rats at 200 (fem ale) or 400 mg/kg (male and female). SD rats did not show evidence of elevated levels of urinary enzymes or increased blood urea nitrogen (BUN) after oral adm inistration of HQ at a dose level of 400 m g/kg. Oral administration of HQ to male and female B6C3F1 mice at 350 mg/kg resulted in only slight but significant increases in BUN.

ISSN:0098-4108    

DOI:10.1080/009841096161861

出版商:Informa UK Ltd    

年代:1996

数据来源: Taylor

摘要:

A comparative evaluation of chelating agents, namely, diethyl dithiocarbamate (DDC), dimethyl dithiocarbamate (DMDC), 1,4,8,11-tetraazacyclotetradecane (CYCLAM), 1,4,8,12- tetraazacyclopentadecane (TACPD), 2,3-dimercaptosuccinic acid (DM SA), and 2,3-dimercapto-1-propane sulfonate (DMPS) was conducted to assess their efficacy against acute cadmium (Cd) toxicity. DMSA and DMPS appeared to be most effective in reducing mortality as well as Cd burden of liver, kidneys, and brain in cadmium intoxicated mice. DMDC reduced Cd levels only in liver and kidneys, while DDC significantly enhanced its level in brain. CYCLAM and TACPD significantly increased the Cd level in liver and kidneys and were ineffective in brain. The therapeutic index as well as therapeutic efficacy was highest for DMSA followed by DMPS and DMDC. A fair degree of correlation was found to exist between (1) stability constant of Cd chelates and percent survival (r=.438), (2) stability constant and percent transport (r=.479), and (3) percent survival and percent transport (r=.447). However, the lipophilicity did not show any appreciable correlation with percent survival and stability constant of Cd chelates.

ISSN:0098-4108    

DOI:10.1080/009841096161870

出版商:Informa UK Ltd    

年代:1996

数据来源: Taylor

摘要:

Previously, we showed that cadmium stimulates the production of glycosaminoglycans (GAGs) but inhibits their sulfation in cultured bovine aortic endothelial cells. The effect of zinc on such alterations of GAGs induced by cadmium was investigated in the present study. The incorporation of [3H]glucosamine and [35S]sulfate into GAGs was determined by the cetylpyridinium chloride precipitation method as a marker of GAG production and GAG sulfation, respectively. The incorporation of both [3H]glucosamine and [35S]sulfate was not changed in GAGs accum ulated in the endothelial cell layer and the conditioned medium after exposure to zinc at 20 mu M or less alone. A simultaneous exposure of the endothelial cell layer to zinc at 20 mu M or less and cadmium at 2 mu M resulted in prevention of the cadmium-induced decrease in [3 5S]sulfate incorporation; however, the cadmium induced increase in [3H]glucosamine incorporation was not affected by zinc. Characterization of GAGs in the cell layer revealed that such an interaction between zinc and cadmium occurred in both heparan sulfate and the other GAGs. Zinc significantly prevented the inhibition of either [3H]thymidineor [3H]leucine incorporation caused by cadmium with less accumulation of intracellular cadmium, suggesting that zinc decreased intracellular cadmium and protected endothelial cells from cadm ium-induced inhibition of DNA and protein synthesis. The present data showed that a simultaneous exposure to cadmium and zinc resulted in an increase in heparan sulfate without a reduction of sulfation in the endothelial cell layer. The alteration may potentiate the antithrombogenic property of vascular endothelium.

ISSN:0098-4108    

DOI:10.1080/009841096161889

出版商:Informa UK Ltd    

年代:1996

数据来源: Taylor

摘要:

Liver tumors from mice treated with genotoxic carcinogens often possess mutations in ras protooncogenes, and these sequence alterations in ras frequently reflect the mutational specificity of the carcinogen. Previous studies suggest that the mouse model used for tumor induction may affect ras mutational patterns. In order to explore this possibility, H- and K ras mutational profiles were established in liver tumors from male B6C3F1 and CD-1 mice administered benzo\[a]pyrene (BaP), 6-nitrochrysene (6-NC), and 4-aminobiphenyl (4-ABP). With the exception of 6-NC-induced tumors in B6C3F1 mice, a high proportion of the tumors induced in both types of mice contained ras mutations. In CD-1 mice, 6-NC predominantly induced C A mutations in H- ras codon 61 (90% of tumors analyzed), whereas 4-ABP mainly induced A T mutations in H- ras codon 61 (50% ) and BaP induced both A T (27%) and G C (50%) mutations in H- ras codon 61 and K- ras codon 13, respectively. In B6C3F1 mice, 85% of BaP tumors had G C mutations in K- ras codon 13 and 85% of 4- ABP tumors had C A mutations in H- ras codon 61, while among 6-NC tumors, only 4% had G C mutations in K- ras codon 13 and none had H- ras mutations. Statistical analysis of these results indicates that the patterns of tumor ras mutations induced by BaP in CD-1 and B6C3F1 mice were indistinguishable, while 6-NC and 4-ABP produced different tumor ras profiles in the two mouse models. Published mutational profiles for active metabolites of BaP and 6-NC from in vitro reporter gene systems were inconsistent with both the CD-1 and B6C3F1 tumor ras mutational responses.

ISSN:0098-4108    

DOI:10.1080/009841096161898

出版商:Informa UK Ltd    

年代:1996

数据来源: Taylor