Cytokines are thought to contribute to the induction of pancreatic beta-cell destruction in insulin-dependent diabetes mellitus. The molecular mechanisms that underlie beta-cell death were investigated by studying cytokine-induced cell death in beta-cell lines. A combination of three cytokines (inte
bcl-2 delay of alkylating agent-induced apoptotic death in a murine hemopoietic stem cell line
✍ Scribed by Leslie J. Fairbairn; Graham J. Cowling; T. Michael Dexter; Joseph A. Rafferty; Geoffrey P. Margison; Birgit Reipert
- Publisher
- John Wiley and Sons
- Year
- 1994
- Tongue
- English
- Weight
- 722 KB
- Volume
- 11
- Category
- Article
- ISSN
- 0899-1987
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✦ Synopsis
Abstract
Many cytotoxic agents kill cells by invoking a specific death pathway termed physiological cell death, or apoptosis. Treatment of a murine hemopoietic stem cell line, FDCP‐mix, with methylmethanesulfonate (MMS) or N′‐methyl‐N′‐nitrosourea (MNU) leads to death by apoptosis. Retroviral gene transfer was used to overexpress the bcl‐2 oncogene in FDCP‐mix cells, and this was associated with a delay in apoptosis in these cells after treatment with MNU and MMS and decreased sensitivity of colony formation to the cytotoxic effects of MMS. These data suggest an explanation for the refractory nature of bcl‐2—expressing follicular lymphoma to cytotoxic chemotherapy and furthermore suggest that DNA‐damaging antitumor therapy may contribute to the progression of disease. ©1994 Wiley‐Liss, Inc.
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