Clastogenic activity of urethane in mice.

Single intraperitoneal (i.p.) treatment of male and female BDF1 (C57B1 x DBA2) mice with urethane (0.5 or 1.0 g/kg) caused a significant increase in micronucleated polychromatic erythrocytes (MNPCE) in bone marrow after 24 h. The clastogenic effect observed was dose-, sex- and age-dependent, the male and younger (6-8 weeks old) animals being more susceptible than the female and older (6 months of age) mice. 3-week oral treatment of female Balb/c mice with urethane (3 g/l added to the drinking water) caused an up to 4-fold increase in the number of micronucleated normochromatic erythrocytes (MNNCE) in mouse peripheral blood. In a month after the carcinogen treatment was stopped, the number of MNNCE dropped to the control values. In addition, a single i.p. treatment of pregnant BDF1 mice on day 17 of gestation with urethane (1.0 g/kg) caused a 514.3% (p less than 0.001) elevation of MNPCE in mouse fetal liver after 24 h as well as a 154.4% (p less than 0.05) increase in MNPCE frequency in the fetal peripheral blood. At this time point, the clastogenic response in mouse fetal liver erythroblasts was less pronounced than that detected in the maternal bone marrow cells. Urethane is a strong clastogen in mice when administered either intraperitoneally or orally and the micronucleus test applied to adult and fetal erythroblasts is a convenient method of choice for studying the acute and subchronic clastogenicity of this carcinogen, its transplacental effects as well as the influence of modifying factors on these processes.     

Polyether urethane urea membrane for an improved hemodialysis.

This paper reviews our current activities of developing polyether urethane urea membranes for hemodialysis application. It is observed that the processing parameters such as precipitation medium, precipitation temperature etc. can influence the porosity of the membrane and subsequently the permeability property. Polyurethane/poly(methyl methacrylate) blended membranes have also shown high permeability. All the membranes are subjected to different sterilization processes and the pore sizes before and after sterilization are determined. The changes in the pore size due to sterilization seems to effect the permeability.     

Hypoventilation after acute phrenicotomy of the urethane anaesthetized rats.

The aim of this study was to explore the mechanism resulting in hypoventilation in rats with denervated diaphragm. Bilateral cervical phrenicotomy (PX) was performed in 15 male rats anaesthetized with urethane (1.3 g/kg i.p.); other 8 rats were sham operated (SX). Ventilation, PaCO2 and the integrated EMG of the external intercostal muscles (iEMG) were measured before and after the surgery, at regular intervals, up to 4 hours postoperatively. During the 4 hours after PX there was a progressive decrease in minute ventilation and an increase in PaCO2 compared with the control values and with that in the SX rats. The increase in PaCO2 was accompanied by an increase in the peak amplitude of the iEMG to 155 +/- 18% of control values after PX and to 228 +/- 33% 4 hours later. Despite the augmented EMG activity tidal volume gradually decreased. The iEMG of the intercostal muscles, however, did not reach a maximum because the shortlasting stimulation of breathing by acute hypercapnia and hypoxia as the result of added dead space (0.5 ml) increased the iEMG still further. These results indicate that both the central and peripheral mechanisms contribute to hypoventilation in anaesthetized rats with denervated diaphragm.     

Isolation of a bacterium that degrades urethane compounds and characterization of its urethane hydrolase

A bacterium which degrades urethane compounds was isolated and identified as Rhodococcus equi strain TB-60. Strain TB-60 degraded toluene-2,4-dicarbamic acid dibutyl ester (TDCB) and accumulated toluene diamine as the degradation product. The enzyme which cleaves urethane bond in TDCB was strongly induced by acetanilide. The purified enzyme (urethane hydrolase) was found to be homogeneous on sodium dodecyl sulfate–polyacrylamide gel electrophoresis. The molecular weight was estimated to be 55 kDa. The optimal temperature and pH were 45°C and 5.5, respectively. The enzyme hydrolyzed aliphatic urethane compound as well as aromatic ones. The activity was inhibited by HgCl₂, p-chrolomercuribenzoic acid, and phenylmethylsulfonyl fluoride, suggesting that cysteine and/or serine residues play an important role in the activity. The enzyme catalyzed the hydrolysis of anilides, amides, and esters as well as TDCB. It was characterized as a novel amidase/esterase, differing in some properties from other known amidases/esterases.     

Strain differences in murine ventilatory behavior persist after urethane anesthesia.

Differences in breathing pattern between awake C57BL/6J (B6) and A/J mice are such that A/J mice breathe slower, deeper, and with greater variability than B6. We theorized that urethane anesthesia, by affecting cortical and subcortical function, would test the hypothesis that strain differences require a fully functional neuroaxis. We anesthetized B6 and A/J mice with urethane, placed them in a whole-body plethysmograph, and measured the durations of inspiration and expiration, respiratory frequency (Fr), and peak amplitude during exposure to room air (21% O2), hyperoxia (5 min, 100% O2), hypoxia (5 min, 8% O2), and posthypoxic reoxygenation (5 min, 100% O2). Breathing variability was assessed by calculating the coefficient of variation (CV) and by applying spatial statistics to Poincaré plots constructed from the timing and amplitude data. Even though Fr in anesthetized B6 and A/J mice was greater than that for unanesthetized animals, anesthetized A/J mice still breathed slower, deeper, and with greater variability than B6 mice at rest and during hyperoxia. During the fourth minute of hypoxia, Fr and its CV were not significantly different between strains. Even though Fr was similar between strains immediately after hypoxia, its CV was significantly greater for B6 than A/J mice. Posthypoxic Fr was significantly less than baseline Fr in B6 but not A/J mice, and the CV for posthypoxic Fr was greater for B6 but less for AJ mice compared with baseline CV. This difference in patterning was confirmed by spatial statistical analysis. We conclude that strain-specific differences in respiratory pattern and its variability are robust genetic traits. The neural substrate for these differences, at least partially, exists within subcortical structures generating the breathing pattern.     

氨基甲酸乙酯水解酶的家族生物信息学分析

氨基甲酸乙酯(Ethyl carbamate,EC)是酒精饮料生产过程中自然产生的副产物,具有潜在的致癌性和遗传毒性,成为影响人们健康的隐患.利用氨基甲酸乙酯水解酶(Urethane hydrolase,UH)消除酒精饮料中已存在的EC具有直接、高效的作用.为了进一步探索EC水解酶的功能与作用,本实验利用生物信息学的方...     

Clastogenic activity of urethane in mice

Single intraperitoneal (i.p.) treatment of male and female BDF1 (C57B1 × DBA2) mice with urethane (0.5 or 1.0 g/kg) caused a significant increase in micronucleated polychromatic erythrocytes (MNPCE) in bone marrow after 24 h. The clastogenic effect observed was dose-, sex- and age-dependent, the male and younger (6–8 weeks old) animals being more susceptible than the female and older (6 months of age) mice. 3-week oral treatment of female Balb/c mice with urethane (3 g/l added to the drinking water) caused an up to 4-fold increase in the number of micronucleated normochromatic erythrocytes (MNNCE) in mouse peripheral blood. In a month after the carcinogen treatment was stopped, the number of MNNCE dropped to the control values. In addition, a single i.p. treatment of pregnant BDF1 mice on day 17 of gestation with urethane (1.0 g/kg) caused a 514.3% (p < 0.001) elevation of MNPCE in mouse fetal liver after 24 h as well as a 154.4% (p < 0.05) increase in MNPCE frequency in the fetal peripheral blood. At this time point, the clastogenic response in mouse fetal liver erythroblasts was less pronounced than that detected in the maternal bone marrow cells. Urethane is a strong clastogen in mice when administered either intraperitoneally or orally and the micronucleus test applied to adult and fetal erythroblasts is a convenient method of choice for studying the acute and subchronic clastogenicity of this carcinogen, its transplacental effects as well as the influence of modifying factors on these processes.     

The metabolism of urethane and related compounds

1. Urethane is metabolized in the rat, rabbit and man by a process of N-hydroxylation. This occurs to a smaller extent when methyl, n-propyl and n-butyl carbamates are administered to the rat and rabbit. 2. Other metabolites which have been detected in urine of animals dosed with urethane and N-hydroxyurethane are ethylmercapturic acid, ethylmercapturic acid sulphoxide and N-acetyl-S-carbethoxycysteine. 3. Substances which appear to be S-ethylglutathione and S-ethylglutathione sulphoxide have been detected in the bile of rats dosed with urethane or N-hydroxyurethane. 4. Methyl, ethyl, n-propyl and n-butyl N-hydroxycarbamates are excreted unchanged in the urine of rats dosed with these compounds to extents depending on the dose administered. 5. Animals dosed with methyl, ethyl, n-propyl or n-butyl carbamate or the corresponding N-hydroxycarbamate excrete the corresponding carbamate and N-hydroxycarbamate in the urine. 6. Methyl, n-propyl and n-butyl carbamates and N-hydroxycarbamates are excreted more slowly than are urethane and N-hydroxyurethane. 7. The probable role of N-hydroxyurethane and the processes of alkylation and carbethoxylation, and of hydroxylamine, nitroxyl and hyponitrous acid in carcinogenesis and chemotherapy with urethane, have been discussed.