目的评价云南省某砒霜厂工人体内砷的代谢转化与 DNA 氧化损伤关系。方法选择云南省某砒霜厂一线工人37例(高暴露组)、管理和后勤人员16例(低暴露组)和当地近期无毒物接触史人员28例(对照组)为研究对象,检测尿中有机砷和8-羟基脱氧鸟苷...目的评价云南省某砒霜厂工人体内砷的代谢转化与 DNA 氧化损伤关系。方法选择云南省某砒霜厂一线工人37例(高暴露组)、管理和后勤人员16例(低暴露组)和当地近期无毒物接触史人员28例(对照组)为研究对象,检测尿中有机砷和8-羟基脱氧鸟苷水平,评价砷的代谢转化和 DNA 氧化损伤相关性。结果高、低暴露组男性尿有机砷分别为(0.48±0.37)mg/L、(0.08±0.05)mg/L,高、低暴露组女性尿有机砷分别为0.11 mg/L、(0.30±0.24)mg/L,对照组均低于检出值下限(0.02 mg/L);高、低暴露组和对照组男性尿8-羟基脱氧鸟苷分别为(18.07±11.68)μmol/mol肌酐、(11.79±8.25)μmol/mol 肌酐和(10.07±3.04)μmol/mol 肌酐,高暴露组高于对照组(P<0.05);高、低暴露组和对照组女性尿8-羟基脱氧鸟苷浓度分别为84.35μmol/mol 肌酐、(21.27±5.89)μmol/mol 肌酐和(14.43±2.58)μmol/mol 肌酐,暴露组女性尿8-羟基脱氧鸟苷浓度高于暴露组男性(P<0.05)。尿中8-羟基脱氧鸟苷浓度随尿中有机砷浓度升高有上升趋势(r_s=0.279,P=0.019)。结论砷职业暴露人群存在明显的 DNA 氧化损伤,对女性损伤更为明显,砷的代谢转化差异可能起关键作用。展开更多
New approaches of making single chain Fv antibodies against O6-methyl-2’ -deoxyguanosine (O6MdG) have been demonstrated by using the phage antibody display system. Using O6MdG as an antigen, 21 positive clones were i...New approaches of making single chain Fv antibodies against O6-methyl-2’ -deoxyguanosine (O6MdG) have been demonstrated by using the phage antibody display system. Using O6MdG as an antigen, 21 positive clones were identified by ELISA from this library, one of which, designated H3, specifically binds to O6MdG with high affinity. The H3 scFv antibody has an affinity constant (Kaff) of 5.94×1011(mol/L)-1. H3 scFv has been successfully used to detect O6MdG in DNA hydrolyses from yeast or E. coli cells treated with a DNA methylating agent. To our knowledge, this is the first report of the selection of a specific scFv against DNA adducts. The results demonstrate the potential applications of the phage display technology for the detection of DNA lesions caused by mutagens and carcinogens.展开更多
Our preliminary studies demonstrated that Metacavir has potential to become a new anti-HBV agent. The main targets of the toxic effects of Metacavir, in rhesus monkeys, were gastrointestinal tracts, liver, blood, and ...Our preliminary studies demonstrated that Metacavir has potential to become a new anti-HBV agent. The main targets of the toxic effects of Metacavir, in rhesus monkeys, were gastrointestinal tracts, liver, blood, and kidneys, which were not related to mitochondrial effects. In this study, the maternal toxicity, embryo-fetal developmental toxicity and teratogenicity were studied in pregnant Sprague-Dawley rats after intragastric administration of Metacavir （200, 100, 50, 0 mg/kg body weight） during the first 6-15 days of pregnancy. Slower weight gain was observed in 5 out of 21 rats subjected to a 200 mg/kg dose, as well as 2 out of 20 subjected to a 100 mg/kg dose. Compared with the solvent control group, the calibration weight gain in the 200 mg/kg and 100 mg/kg dosage groups respectively, during first 6-20 pregnant days were significantly different （P 〈 0.01, P 〈 0.05）. Significant dose related adverse effects to other reproductive parameters were not seen in F0 and F1, but the number of stillbirths in high dose group showed notably difference compared with the control group （P 〈 0.05）, while the litter incidence showed no difference. No Metacavir-associated pathological changes were observed. The present research indicated that at a dose of 200 mg/（kg·d） （i.e., 40 times the effective dose in rats）, Metacavir shows some maternal toxicity to SD rats. The embryotoxicity in the 200 mg/kg group encompass decreased fetal body weight, and higher fetal mortality rates, compared with the control group. However, the litter incidence showed no statistical difference. All the treated rats displayed normal bone development, no teratogenicity and without adverse effects on fetal development, thus indicating that below a dose of 200 mg/（kg· d） there is no teratogenic side effects.展开更多
文摘目的评价云南省某砒霜厂工人体内砷的代谢转化与 DNA 氧化损伤关系。方法选择云南省某砒霜厂一线工人37例(高暴露组)、管理和后勤人员16例(低暴露组)和当地近期无毒物接触史人员28例(对照组)为研究对象,检测尿中有机砷和8-羟基脱氧鸟苷水平,评价砷的代谢转化和 DNA 氧化损伤相关性。结果高、低暴露组男性尿有机砷分别为(0.48±0.37)mg/L、(0.08±0.05)mg/L,高、低暴露组女性尿有机砷分别为0.11 mg/L、(0.30±0.24)mg/L,对照组均低于检出值下限(0.02 mg/L);高、低暴露组和对照组男性尿8-羟基脱氧鸟苷分别为(18.07±11.68)μmol/mol肌酐、(11.79±8.25)μmol/mol 肌酐和(10.07±3.04)μmol/mol 肌酐,高暴露组高于对照组(P<0.05);高、低暴露组和对照组女性尿8-羟基脱氧鸟苷浓度分别为84.35μmol/mol 肌酐、(21.27±5.89)μmol/mol 肌酐和(14.43±2.58)μmol/mol 肌酐,暴露组女性尿8-羟基脱氧鸟苷浓度高于暴露组男性(P<0.05)。尿中8-羟基脱氧鸟苷浓度随尿中有机砷浓度升高有上升趋势(r_s=0.279,P=0.019)。结论砷职业暴露人群存在明显的 DNA 氧化损伤,对女性损伤更为明显,砷的代谢转化差异可能起关键作用。
基金This work was supported by the President Grant of the Chinese Academy of Sciences and K.C. Wong Education Founda-tion (Hong Kong) to HD., and also by the Natural Sciences and Engineering Research Council of Canada (Grant No. OGPO 138338 to WX).
文摘New approaches of making single chain Fv antibodies against O6-methyl-2’ -deoxyguanosine (O6MdG) have been demonstrated by using the phage antibody display system. Using O6MdG as an antigen, 21 positive clones were identified by ELISA from this library, one of which, designated H3, specifically binds to O6MdG with high affinity. The H3 scFv antibody has an affinity constant (Kaff) of 5.94×1011(mol/L)-1. H3 scFv has been successfully used to detect O6MdG in DNA hydrolyses from yeast or E. coli cells treated with a DNA methylating agent. To our knowledge, this is the first report of the selection of a specific scFv against DNA adducts. The results demonstrate the potential applications of the phage display technology for the detection of DNA lesions caused by mutagens and carcinogens.
文摘Our preliminary studies demonstrated that Metacavir has potential to become a new anti-HBV agent. The main targets of the toxic effects of Metacavir, in rhesus monkeys, were gastrointestinal tracts, liver, blood, and kidneys, which were not related to mitochondrial effects. In this study, the maternal toxicity, embryo-fetal developmental toxicity and teratogenicity were studied in pregnant Sprague-Dawley rats after intragastric administration of Metacavir （200, 100, 50, 0 mg/kg body weight） during the first 6-15 days of pregnancy. Slower weight gain was observed in 5 out of 21 rats subjected to a 200 mg/kg dose, as well as 2 out of 20 subjected to a 100 mg/kg dose. Compared with the solvent control group, the calibration weight gain in the 200 mg/kg and 100 mg/kg dosage groups respectively, during first 6-20 pregnant days were significantly different （P 〈 0.01, P 〈 0.05）. Significant dose related adverse effects to other reproductive parameters were not seen in F0 and F1, but the number of stillbirths in high dose group showed notably difference compared with the control group （P 〈 0.05）, while the litter incidence showed no difference. No Metacavir-associated pathological changes were observed. The present research indicated that at a dose of 200 mg/（kg·d） （i.e., 40 times the effective dose in rats）, Metacavir shows some maternal toxicity to SD rats. The embryotoxicity in the 200 mg/kg group encompass decreased fetal body weight, and higher fetal mortality rates, compared with the control group. However, the litter incidence showed no statistical difference. All the treated rats displayed normal bone development, no teratogenicity and without adverse effects on fetal development, thus indicating that below a dose of 200 mg/（kg· d） there is no teratogenic side effects.
