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Kenneth S. Ramos Kathryn K. McMahon Celestine Alipui Diane Demick 《Cell biology and toxicology》1991,7(2):111-128
Studies were conducted to determine if in vivo exposure to dinitrotoluenes (DNT), which is associated with circulatory disorders of atherosclerotic etiology in humans, is associated with alterations of vascular smooth muscle cells (SMC) consistent with the atherogenic process. Sprague-Dawley rats (150-180 g) were injected IP for 5 days/week for 8 weeks with 2,4- or 2,6-DNT (0.5, 5, or 10 mg/kg) or medium chain triglyceride (MCT) oil. Histopathologic evaluation of aortae from animals exposed to either isomer showed dysplasia and rearrangement of SMC at all doses tested. Reduced 3H-thymidine incorporation was observed in primary cultures of aortic SMC from DNT-exposed animals relative to vehicle controls. This inhibitory response was maintained for up to two passages in culture after which a significant increase in thymidine incorporation was observed. Exposure of SMC from naive animals to DNT in vitro (1–100 µM) did not alter the extent of thymidine incorporation in cycling or growth-arrested cultures. In contrast, exposure to 2,4- or 2,6-diaminotoluene (DAT) (1–100 µM), carcinogens which share toxic metabolic intermediates in common with DNT, inhibited replicative DNA synthesis and stimulated unscheduled DNA synthesis in cycling and growth-arrested cultures of SMC, respectively. Our results suggest that modulation of DNA synthesis in aortic SMC by DNT metabolites generated in vivo contribute to the development of vascular lesions.Abbreviation DAT
diaminotuluene
- tDNT
technical grade dinitrotoluene
- DNT
dinitrotoluenes
- HU
hydroxyurea
- IP
intraperitoneal
- LDH
lactate dehydrogenase
- MCT oil
medium chain triglyceride
- NPTC
non-protein thiol content
- RDS
replicative DNA synthesis
- SEM
standard error of the mean
- SMC
smooth muscle cells
- UDS
unscheduled DNA synthesis 相似文献
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OBJECTIVE: To relate the sizes of general practice catchment areas in one London borough to list size, deprivation payments, medical staffing, and locally and nationally recognised measures of quality. DESIGN: Study of general practice catchment area maps. SETTING: London borough of Lambeth. SUBJECTS: 60 out of the 71 general practices in Lambeth. MAIN OUTCOME MEASURES: Practice catchment area size with corrections for numbers of doctors and patients. RESULTS: Catchment area size varied greatly between practices, showing an almost 150-fold difference between the largest and smallest practices. This size differential was even more marked when the size of the catchment area was corrected for the number of general practitioners in the practice, where a 300-fold difference was found. Substantial differences existed between practices in each of the four locally assigned quality bands. The weakest practices had catchment areas three times as large as those of the strongest practices. When corrected for medical staffing, the difference was eight times as great. A calculated measure of patient dispersion showed that the practice population of the strongest practices was four times as densely clustered as that of the weakest practices, whose patients were more widely geographically dispersed. CONCLUSIONS: Large variations exist in the size of catchment areas of inner city practices even when corrected for numbers of doctors and patients. These differences are associated with variations in quality of care. 相似文献
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