Mechanisms of cell death induced by 5-fluoro-2'-deoxyuridine (FUdR)--necrosis or apoptosis after treated with FUdR.

Yusuke Uchikubo, Takako Hasegawa, Saeko Mitani, Hye-Sook Kim, Yusuke Wataya

Research output: Chapter in Book/Report/Conference proceedingChapter

3 Citations (Scopus)

Abstract

5-Fluoro-2'-deoxyuridine (FUdR) inhibits thymidylate synthase (TS). The inhibition of TS causes an imbalance of intracellular deoxyribonucleoside triphosphate (dNTP) pools which subsequently induced cell death. We investigated the molecular mechanisms of cell death after treated with FUdR in F28-7 strain (which induced necrosis) and F28-7-A strain (mutant of F28-7 strain which induced apoptosis). After treated with FUdR, we observed different size of DNA fragmentations. F28-7 strain induced DNA cleavaged into 100-200 kbp fragments and F28-7-A strain induced DNA cleavaged into oligonucleosomal sized fragments. In F28-7 strain, FUdR induced the increased mRNA level of c-jun, c-fos and c-myc genes, caspase-3 like protease activity and the changes of mitochondrial membrane potential which were greater and earlier than those of F28-7-A strain. On the other hand, F28-7-A strain induced release of cytochrome c from mitochondrial, but not F28-7 strain. Furthermore, caspase-5 inhibitor was strongly inhibited the cell death of F28-7 strain. We suggest that it is concerned with intensity of intracellular signals in the cell death of F28-7 strain and F28-7-A strain.

Original languageEnglish
Title of host publicationNucleic acids research. Supplement (2001)
Pages245-246
Number of pages2
Edition2
Publication statusPublished - 2002

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Uchikubo, Y., Hasegawa, T., Mitani, S., Kim, H-S., & Wataya, Y. (2002). Mechanisms of cell death induced by 5-fluoro-2'-deoxyuridine (FUdR)--necrosis or apoptosis after treated with FUdR. In Nucleic acids research. Supplement (2001) (2 ed., pp. 245-246)