| 1. |
- von Bültzingslöwen, Inger, 1947, et al.
(författare)
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5-Fluorouracil induces autophagic degeneration in rat oral keratinocytes.
- 2001
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Ingår i: Oral oncology. - 1368-8375. ; 37:6, s. 537-44
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we investigated the effect of 5-fluorouracil (5-FU) on the keratinocytes of oral epithelium. Female Lewis rats were given 5-FU i.v. and were killed 12, 24 or 36 h after injection. The buccal mucosa was dissected. The number of nuclei with DNA strand breaks and the total number of nuclei per volume of the epithelial basal cell layer was estimated using terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-biotin nick end labeling. Epithelial cells were analysed by flow cytometry, transmission electron microscopy and a dye exclusion test. The number of cells with DNA strand breaks increased in 5-FU treated rats. Flow cytometry showed a decrease in cell size and an increase in granularity with increasing doses of 5-FU. Dye exclusion gave no indication of degenerate cell membranes. By transmission electron microscopy, the cells showed evidence of degeneration, shrinkage and loss of cell-to-cell contact. Vacuolation was extensive and, in contrast to apoptotic cells, nuclear chromatin condensation seemed to occur centrally in the nuclei. The results show that 5-FU treatment in vivo induces alterations in rat oral keratinocytes that are consistent with autophagic degeneration.
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| 2. |
- von Bültzingslöwen, Inger, 1947, et al.
(författare)
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Effects of 5-fluorouracil on mitogen-induced costimulatory capacity of accessory cells from rat oral mucosa and dental pulp.
- 2001
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Ingår i: Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. - 0904-2512. ; 30:6, s. 362-7
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Tidskriftsartikel (refereegranskat)abstract
- The present study was designed to investigate the effect of the antimetabolite 5-fluorouracil (5-FU) on the capacity of the oral epithelium and the dental pulp to induce a mitogen-driven T-cell proliferation. Inbred Lewis rats were given 6 i.v. injections of 5-FU (30 mg/kg or 50 mg/kg) over a period of 8 days. Suspensions of oral epithelial and dental pulpal cells were prepared. The costimulatory capacity of the accessory cells from treated animals was monitored by their ability to induce a mitogen (ConA)-mediated proliferation of T cells isolated from regional lymph nodes of untreated animals. Accessory epithelial cells from rats treated with the high dose of 5-FU, but not the low dose, induced a decreased T-cell proliferation compared to controls. Accessory pulpal cells from rats, treated with 30 mg/kg or 50 mg/kg of 5-FU, induced a lower T-cell proliferation. When MHC class II molecule depleted T-cell suspensions from lymph nodes of 5-FU-injected animals were incubated with ConA, a significant proliferative response was observed. This finding correlated with an increase of MHC class II molecule expressing cells detected after incubation, although no such cells were observed immediately following the initial purification step of T cells. This finding demonstrates that the accessory cells could partly restore their expression of MHC class II molecules during incubation. The results of the study suggest that the function of immunocompetent cells of the oral mucosa and dental pulp is influenced by treatment with 5-FU and that the function of accessory cells of the pulp is affected more than the function of accessory cells derived from the oral mucosa.
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| 3. |
- von Bültzingslöwen, Inger, 1947
(författare)
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Effects of 5-fluorouracil on oral barrier functions
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Many anticancer drugs, e.g. 5-fluorouracil (5-FU), may cause oral mucositis and ulcerations. These adverse reactions can be severe and debilitating to the patient, and adjustment of the cancer treatment may be necessary. Efforts to develop reliable clinical protocols to relieve the oral side effects have so far been disappointing. Thus, further knowledge regarding the pathophysiology behind these lesions is warranted. This thesis focused on some influences of 5-FU on major oral barrier functions, the oral epithelium, the local immune defence and the microflora. Rats were treated with 5-FU (30 mg/kg; 50 mg/kg) i.v. In one experiment, the probiotic bacteria Lactobacillus plantarum 299v, was delivered in the drinking water during 5-FU treatment, to modify bacterial overgrowth. After the animals were sacrificed, biopsies were taken. Oral keratinocytes were investigated for 5-FU induced mode of cell death. Analysis was performed by flow cytometry, vital dye exclusion test, the TUNEL method and ultrastructural analysis. The number of local immunocompetent cells of the oral mucosa was compared with the number of similar cell populations of the dental pulp. MHC class II molecule expressing cells of the buccal epithelium and dental pulp were assessed for the capacity to induce a ConA stimulated T cell proliferation. Changes in bacterial homeostasis of the oral cavity and intestine were evaluated and predominating groups of facultative anaerobes were identified by colony morphology and gram staining appearance. The cervical and mesenteric lymph nodes were analysed for any numbers of viable bacteria. 5-FU treatment caused alterations in the keratinocytes consistent with autophagic degeneration. The local cellular immune defence of the oral mucosa and dental pulp was affected. 5-FU caused an increase in the total number of bacteria and the number of facultative anaerobes in the oral cavity and in the number of facultative anaerobes in the intestine. The proportions of facultative gram-negative rods increased. Bacteria increased in numbers in both the cervical and mesenteric lymph nodes. These findings reinforce the oral cavity, along with the gastrointestinal tract, as an important source for bacterial dissemination. L. plantarum 299v did to some extent normalise 5-FU induced disturbances in the oral and intestinal microbiota and improve the well-being of the animals. Conclusions: Influences of 5-FU on oral barrier functions were demonstrated. 5-FU may disrupt the oral epithelium, decrease the immune response and disturb the microflora. The findings indicate that the cervical lymph nodes may be an important route for bacterial dissemination from the oral cavity. Probiotic bacteria may have a positive effect on some of these functions.
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| 4. |
- von Bültzingslöwen, Inger, 1947, et al.
(författare)
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Oral and intestinal microflora in 5-fluorouracil treated rats, translocation to cervical and mesenteric lymph nodes and effects of probiotic bacteria.
- 2003
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Ingår i: Oral microbiology and immunology. - 0902-0055. ; 18:5, s. 278-84
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Tidskriftsartikel (refereegranskat)abstract
- Serious systemic infections may occur during cancer chemotherapy due to disturbances in the oropharyngeal and gastrointestinal microflora, impaired mucosal barrier functions and immunosuppression. Bacteria may spread from the gastrointestinal tract to the regional lymph nodes. The routes for bacterial spread from the oral cavity are less well known. In the present study we investigated changes in the oral and intestinal microfloras in rats given 50 mg/kg 5-fluorouracil (5-FU) i.v. for 6 days. Bacterial dissemination to the lymph nodes draining the oral cavity and the lymph nodes draining the gastrointestinal tract was examined. Effects of adding the probiotic strain Lactobacillus plantarum 299v in the drinking water to the rats were measured. 5-FU treatment caused an increase in the number of facultative and strictly anaerobic bacteria in biopsies from the oral cavity and an increase in the number of facultative anaerobes in the large intestine. The proportion of facultative gram-negative rods increased in both the oral cavity and intestine. Bacteria translocated to both the cervical and mesenteric lymph nodes in untreated animals and increased in numbers after 5-FU treatment due to an increase in the number of facultative gram-negative rods. Treatment with L. plantarum 299v improved food intake and body weight in 5-FU-treated rats. It also reduced the 5-FU-induced raise in the total numbers of facultative anaerobes in the intestine, but did not reduce translocation and did not prevent diarrhea. This study reinforces the oral cavity, along with the gastrointestinal tract, as a source for bacterial dissemination. The use of probiotic bacteria may reduce some side effects of 5-FU treatment.
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