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101.
Xu Dai-gen He Han-zhen Zhang Guo-gao B. Gansewendt H. Peter H. M. Bolt 《华中科技大学学报(医学英德文版)》1993,13(2):100-104
Monohalogenated methanes (methyl chloride, methyl bromide and methyl iodide) are mutagenic and carcinogenic. The possible mechanism of these effects, DNA methylation, was studied. DNA adducts from orgnas of F344 rats exposed to these chemicals were separated and identified with high performance liquid chromatography (HPLC) and gaschro-matography/massspectrometry (GC/ MS). DNA adducts, 7-methylguanine (7-MeG) and O6-Methylguanine(08-MeG), incorporation of14C into de novo synthesis of nucleobases could be observed in enzymatic DNA hydrolysates by HPLC and determination of the radioactivity in the fractions. The formation of DNA add,ue,ts in the studied organs was only quantitatively different. The formation of O6-MeG was further pioved by analysing the acidic hydrolysates using HPLC with non-radioactive O6MeG as internal standard. 7-MeG and 3-MeA were identified with GC/MS analysis. 相似文献
102.
103.
Peter Chiba Barbara Tell Walter Jger Elisabeth Richter Manuela Hitzlera Gerhard Ecker 《Archiv der Pharmazie》1997,330(11):343-347
A series of 5-hydroxy and 5-benzyloxy analogs of the antiarrhythmic and multidrug resistance (MDR) modulating drug propafenone was synthesized and the MDR-modulating activity of the compounds was evaluated using a daunomycin efflux assay system. The key step of the synthesis is the selective reduction of the double bond in 1 without cleavage of the benzyl group thus leading to the phenol 3 . Alkylation with epichlorohydrine followed by nucleophilic epoxide ring opening gave the benzylated target compounds 5a–d . Subsequent cleavage of the benzyl group gave the 5-hydroxy analogs 6a–d . Structure activity relationship studies showed, that the 5-hydroxy derivates 6a–d fit the log P/log potency correlation line previously established for a series of propafenone analogs. In contrast, all four 5-benzyloxy analogs 5a–d showed almost identical EC50 values, independent of their log P value. 相似文献
104.
105.
106.
107.
Hydroxylation of chlorzoxazone as a specific probe for human liver cytochrome P-450IIE1 总被引:10,自引:0,他引:10
R Peter R B?cker P H Beaune M Iwasaki F P Guengerich C S Yang 《Chemical research in toxicology》1990,3(6):566-573
Human cytochrome P-450IIE1 has been implicated in the oxidation of a number of substrates, including protoxins and -carcinogens. To date, no drugs have been identified that are exclusive substrates for the protein and are applicable for use as noninvasive probes of the in vivo function of the enzyme in humans. Chlorzoxazone was found to be oxidized only to 6-hydroxychlorzoxazone in human liver microsomes. Results of steady-state kinetics are consistent with the view that only a single enzyme catalyzes the reaction. The microsomal reaction was strongly inhibited by rabbit anti-P-450IIE1 and, in a competitive manner, by known P-450IIE1 substrates. Rates of chlorzoxazone 6-hydroxylation in different human liver microsomal preparations were well correlated with levels of immunochemically measured P-450IIE1 and rates of (CH3)2NNO oxidation. Chlorzoxazone 6-hydroxylation was also found to be catalyzed by purified human liver P-450IIE1. These results provide strong evidence that P-450IIE1 is the primary catalyst of chlorzoxazone 6-hydroxylation in human liver. Rates of chlorzoxazone 6-hydroxylation vary considerably among human liver samples, and chlorzoxazone 6-hydroxylation may have potential use as a noninvasive probe in estimating the in vivo expression of human P-450IIE1 and its significance as a risk factor in the toxicity and carcinogenicity of a number of solvents, nitrosamines, and drugs. 相似文献
108.
Wolfgang Söllner Gerlinde Mairinger Martina Zingg-Schir Peter Fritsch 《Der Hautarzt; Zeitschrift für Dermatologie, Venerologie, und verwandte Gebiete》1996,47(3):200-205
Zusammenfassung
Bei 205 Melanompatienten im Stadium I und II wurden das Ausma? der psychosozialen Belastung und der sozialen Unterstützung
sowie die Einstellung der Patienten zu unterstützenden Gespr?chsangeboten erhoben. 59% der Patienten fanden zus?tzliche unterstützende
Gespr?che mit dem behandelnden Dermatologen, 20% mit einem Psychotherapeuten sinnvoll. Patienten, die starke Angst vor einem
Fortschreiten des Tumors ?u?erten und die sich über die Erkrankung nicht ausreichend aufgekl?rt fühlten, wünschten Gespr?che
mit dem behandelnden Arzt. Patienten, die sich psychosozial st?rker belastet fühlten und sozial weniger Unterstützung durch
ihr soziales Umfeld angaben, befürworteten Unterstützung durch einen Psychotherapeuten. Auch eine ungünstige Prognose scheint
das Interesse an psychotherapeutischer Unterstützung zu verst?rken.
Eingegangen am 13. Januar 1995 Angenommen am 23. August 1995 相似文献
109.
Timothy Threlfall Neil Kent Peter Garcia-Webb Elizabeth Byrnes Paul Psaila-Savona 《Australian and New Zealand journal of public health》1993,17(4):379-381
Abstract: This study reports on an analysis of the lead concentrations in 123 venous blood samples collected from Perth children aged between two months and 17 years attending Princess Margaret Hospital. The overall geometric mean was 6.9 μg lead per 100 ml whole blood, with 95 per cent of results lying between 3.2 and 14.8 μg/100 ml. Among children under five years of age, those aged between 18 months and two years had the highest geometric mean blood lead (11.1 μg/100 ml). There were no consistent associations between geometric mean blood lead and area of residence, age group or sex. In this sample of Perth children, the mean blood lead concentration was lower than those reported in other studies. Less than 0.1 per cent of children of the age range studied would have been expected to have lead levels exceeding the NHMRC ‘level of concern’ (25 μg/100 ml) current at the time of the study. However, the recent adoption of goal of less than 10 μg/100 ml could mean that lead levels in up to 21 per cent of Perth children would now be regarded as excessive. 相似文献
110.