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Inhibition of 2-nitropropane-induced rat liver DNA and RNA damage by benzyl selenocyanate 总被引:5,自引:2,他引:3
We observed that pretreatment of male F344 rats with benzyl selenocyanate,
a versatile organoselenium chemopreventive agent in several animal model
systems, decreases the levels of DNA and RNA modifications produced in the
liver by the hepatocarcinogen 2- nitropropane. To clarify the mechanisms
involved, we pretreated male F344 rats with either benzyl selenocyanate,
its sulfur analog benzyl thiocyanate, phenobarbital or cobalt
protoporphyrin IX; the latter is a depletor of P450. We then determined (1)
the ability of liver microsomes to denitrify 2-nitropropane, (2) effects on
2-nitropropane- induced liver DNA and RNA modifications and (3) amount of
nitrate excreted in rat urine following administration of the carcinogen.
Pretreatment with benzyl selenocyanate or phenobarbital increased the
denitrification activity of liver microsomes by 217 and 765%, respectively,
increased liver P4502B1 by 31- and 435-fold, respectively, decreased the
levels of 2-nitropropane-induced modifications in liver DNA (29-70% and
17-30%, respectively) and RNA (67-85% and 30-50%, respectively), and
increased the 24-h urinary excretion of nitrate by 157 and 209%,
respectively. Pretreatment with benzyl thiocyanate had no significant
effect on any of these parameters. Pretreatment with cobalt protoporphyrin
IX decreased liver P4502B 1 by 87%, decreased the denitrification activity
of liver microsomes by 76%, decreased the 24 h urinary excretion of nitrate
by 88.5%, but increased the extent of 2-nitropropane-induced liver nucleic
acid modifications by 17-67%. These results indicate that the metabolic
sequence from 2-nitropropane to the reactive species causing DNA and RNA
modifications does not involve the removal of the nitro group. Moreover,
they suggest that benzyl selenocyanate inhibits 2-NP-induced liver nucleic
acid modifications in part by increasing its detoxication through induction
of denitrification, although it is evident that other mechanisms must also
be involved.
相似文献
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Abruzzo LV; Schmidt K; Weiss LM; Jaffe ES; Medeiros LJ; Sander CA; Raffeld M 《Blood》1993,82(1):241-246
We describe a patient with angioimmunoblastic lymphadenopathy with dysproteinemia (AILD), who subsequently developed large-cell immunoblastic lymphoma of B-cell immunophenotype. At the time of the initial diagnosis, histologic examination of an inguinal lymph node showed typical features of AILD, and there was no evidence of a monoclonal B-cell population by immunohistochemical analysis. In situ hybridization and Southern blot analysis for Epstein-Barr virus (EBV) were negative. At autopsy 2 years later, the patient had widespread lymph node and organ involvement by large-cell immunoblastic lymphoma of B-cell immunophenotype. Southern blot analysis performed on DNA extracted from lymph nodes, liver, and spleen showed two patterns of Ig heavy chain and kappa light chain gene rearrangements. The T-cell receptor beta chain gene was in the germline configuration. Analysis with an EBV terminal repeat region probe showed two clonal populations that paralleled the Ig gene rearrangement studies. Double-labeling immunohistochemistry and in situ hybridization confirmed the presence of EBV within the neoplastic B cells. The data support the hypothesis that EBV was not etiologically related to AILD in this case, and that EBV proliferation may occur after the onset of the disease. Further, the data suggest that some B-cell lymphomas that arise in the setting of AILD resemble EBV-associated B-cell lymphomas that arise in other immunodeficiency states. 相似文献
7.
Histamine reduces boron neutron capture therapy‐induced mucositis in an oral precancer model
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Nicola Napoli Elsa S. Strotmeyer Kristine E. Ensrud Deborah E. Sellmeyer Douglas C. Bauer Andrew R. Hoffman Thuy-Tien L. Dam Elizabeth Barrett-Connor Lisa Palermo Eric S. Orwoll Steven R. Cummings Dennis M. Black Ann V. Schwartz 《Diabetologia》2014,57(10):2057-2065
Aims/hypothesis
Diabetes mellitus is associated with increased fracture risk in women but few studies are available in men. To evaluate the relationship between diabetes and prospective non-vertebral fractures in elderly men, we used data from the Osteoporotic Fractures in Men (MrOS) study.Methods
The MrOS enrolled 5,994 men (aged ≥65 years). Diabetes (ascertained by self-report, the use of medication for diabetes or an elevated fasting glucose level) was reported in 881 individuals, 80 of whom were using insulin. Hip and spine bone mineral density (BMD) was measured using dual x-ray absorptiometry (DXA). After recruitment, the men were followed for incident non-vertebral fractures using a triannual (3 yearly) questionnaire for an average of 9.1 (SD 2.7) years. The Cox proportional hazards model was used to assess the incident risk of fractures.Results
In models adjusted for age, race, clinic site and total hip BMD, the risk of non-vertebral fracture was higher in men with diabetes compared with normoglycaemic men (HR 1.30, 95% CI 1.09, 1.54) and was elevated in men using insulin (HR 2.46, 95% CI 1.69, 3.59). Men with impaired fasting glucose did not have a higher risk of fracture compared with normoglycaemic men (HR 1.04, 95% CI 0.89, 1.21). After multivariable adjustment, the risk of non-vertebral fracture remained higher only among men with diabetes who were using insulin (HR 1.74, 95% CI 1.13, 2.69).Conclusions/interpretation
Men with diabetes who are using insulin have an increased risk of non-vertebral fracture for a given age and BMD. 相似文献9.
Valéria Martins Araújo CARNEIRO Ana Cristina Barreto BEZERRA Maria do Carmo Machado GUIMAR?ES Maria Imaculada MUNIZ-JUNQUEIRA 《Journal of applied oral science : revista FOB》2012,20(5):503-509
Phagocytosis by neutrophils and monocytes constitutes the main defense mechanism
against bacterial challenges in periodontitis. Phagocytosis by neutrophils has
already been evaluated, whereas phagocytic function of monocytes has hardly been
addressed so far.
Objectives
The aim of this study was to assess phagocytosis by neutrophils and monocytes in periodontitis.Material and Methods
The sample included 30 subjects with severe periodontitis and 27 control subjects without periodontal disease. The phagocytic index (PhI) was calculated as the mean number of adhered/ingested Saccharomyces cerevisiae per phagocytozing monocyte or neutrophil multiplied by the percentage of phagocytes involved in phagocytosis.Results
A significant reduction in phagocyte functions was observed in individuals with periodontitis. The median of PhI of neutrophils using non-sensitized S. cerevisiae was 3 for the control group, and 1.5 for the periodontitis group (p=0.01, Mann-Whitney test). The median of PhI of monocytes with non-sensitized S. cerevisiae was 26.13 for the control group, and 13.23 for the periodontitis group (p=0.03, Mann Whitney test). The median of PhI of monocytes assessed with sensitized S. cerevisiae was 97.92 for the control group and 60.1 for the periodontitis group (p=0.005, t-test).Conclusion
The data demonstrated a reduction in the function of phagocytes, suggesting a decrease in immune defenses in periodontitis. 相似文献10.
Camila Santos PEREIRA Marcos Vinícius Macedo de OLIVEIRA Lucas Oliveira BARROS Gabriela Alencar BANDEIRA Sérgio Henrique Sousa SANTOS John R. BASILE André Luiz Sena GUIMAR?ES Alfredo Maurício Batista DE PAULA 《Journal of applied oral science : revista FOB》2013,21(5):416-421