Abstract
Apoptosis is a highly regulated and programmed cell breakdown process characterized by numerous changes. It was reported as the major mechanism of anticancer drug-induced cells death. Unfortunately, many of these drugs are non-specific and cause severe side effects. The effects of 5-flourouracil (5-FU) on the apoptotic events in normal murine thymus were evaluated using an in vivo model. A single dose of 5-FU (150 mg/kg ip) was injected to CF-1 mice. A multiparametric analysis of thymic weight, cellularity, viability, architectural organization, apoptosis, DNA fragmentation, and the expression of several apoptotic proteins was evaluated in 10 days time-course study post-5-FU dosing. Total organ weights, thymocyte counts, and cell viabilities diminished drastically from the second day. The thymus architecture assessed through electron scanning microscopy revealed deep alterations and the lost of cell–cell contact between the first and the third days. DNA fragmentation and apoptotic indexes (May Grünwald Giemsa staining, double flourescent dyes, and TdT-mediated dUTP nick-end labeling assay) revealed that cell death was maximal on the second day (three times over control). Furthermore, the pro-apoptotic proteins FAS and Bax were strongly up-regulated during the first 2 days. The aforementioned morphological and biochemical changes were also accompanied within the same period by caspase 3 activation. This study revealed that in vivo apoptosis in normal thymus after 5-FU administration is related to FAS, Bax, and Caspase 3 co-expressions under the current experimental conditions, these findings, therefore, contribute to a new insight into the molecular mechanisms involved during 5-FU administration upon the thymus and the possible events committed in the lymphophenia associated with chemotherapy.
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Aquino Esperanza, J.A. et al. (2008). In vivo 5-flourouracil-induced apoptosis on murine thymocytes: involvement of FAS, Bax and Caspase3. In: Hunt, C. (eds) Proceedings of the VIIIth Conference of the International Society for Trace Element Research in Humans (ISTERH), the IXth Conference of the Nordic Trace Element Society (NTES), and the VIth Conference of the Hellenic Trace Element Society (HTES), 2007. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-9056-1_11
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DOI: https://doi.org/10.1007/978-1-4020-9056-1_11
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