Disease relevance of Rapop1

• Protease inhibitors restore radiation-induced apoptosis to Bcl-2-expressing lymphoma cells [1].
• We also used an in vivo approach to enforce intermittent hypoxia in tumor-bearing mice and found that it was associated with less radiation-induced apoptosis within both the vascular and the tumor cell compartments (versus normoxia or prolonged hypoxia) [2].
• Radiation-induced apoptosis in human sarcoma and glioma cell lines [3].
• CONCLUSIONS: Inhibition of NF-kappaB activation increases radiation-induced apoptosis and enhances radiosensitivity in colorectal cancer cells in vitro and in vivo [4].
• Radiation-induced apoptosis in F9 teratocarcinoma cells [5].

High impact information on Rapop1

• Acid sphingomyelinase-deficient human lymphoblasts and mice are defective in radiation-induced apoptosis [6].
• p53 is required for radiation-induced apoptosis in mouse thymocytes [7].
• Cyclooxygenase-2 (COX-2) expression is translationally silenced in epithelial cells undergoing radiation-induced apoptosis [8].
• However, anti-TSA-1 did not block either steroid- or radiation-induced apoptosis, indicating that a signal via TSA-1 does not inhibit a common pathway of thymocyte apoptosis [9].
• Our in vivo studies indicate that there are bax-dependent and bax-independent radiation-induced apoptosis in the intestine but that only the bax-dependent apoptosis is reduced by dmPGE2 [10].

Chemical compound and disease context of Rapop1

• To analyze specific genes related to radiation-induced apoptosis, 12 apoptosis-resistant clones were isolated from cells of the radiosensitive mouse thymic lymphoma 3SB line after treatment with ethyl methanesulfonate [11].
• Effect of a hypoxic cell sensitizer doranidazole on the radiation-induced apoptosis of mouse L5178Y lymphoma cells [12].
• The aims of this study were to investigate whether gemcitabine could enhance radiation-induced tumor regrowth delay in a human squamous carcinoma (FaDu) xenograft in nude mice and to examine the effect of gemcitabine on radiation-induced apoptosis in in vivo tumors [13].

Biological context of Rapop1

• The STS/A (STS) allele at Rapop1 leads to decreased sensitivity to apoptosis in the BALB/cHeA (BALB/c) background [14].
• In the present study, we established Rapop1 congenic strains C.S-R1 and C.S-R1L, which contain the STS genome in a 0.45 cM interval critical for Rapop1 in common in the BALB/c background [14].
• Recently, we mapped a novel apoptosis susceptibility gene Rapop1 (radiation-induced apoptosis 1) to chromosome 16 (N. Mori et al., 1995, Genomics 25: 604-614) [15].
• Variations in Prkdc encoding the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) and susceptibility to radiation-induced apoptosis and lymphomagenesis [14].
• Cell cycle analysis showed a G(2) delay and no increase in radiation-induced apoptosis in the cells treated with IR or roscovitine and IR [16].

Anatomical context of Rapop1

• Although these two loci may be identical to Rapop1 and Rapop2, they affect apoptosis in colon in a way different from that in thymus [17].
• Radiation-induced apoptosis in peritoneal resident macrophages of C3H mice [18].
• Transformation with activated Src rather than Ras rendered fibroblasts selectively resistant to adhesion-dependent apoptosis, an effect likely related to Src's role in integrin signaling, while simultaneously sensitizing the cells to radiation-induced apoptosis [19].
• Atm and Bax cooperate in ionizing radiation-induced apoptosis in the central nervous system [20].
• We studied the role of the transcription factor NF-kappaB in protection against radiation-induced apoptosis in the intestinal epithelium in vivo [21].

Associations of Rapop1 with chemical compounds

• In contrast, treatment with either cysteine, cysteamine or RibCys for 20 h beginning 60 min after irradiation enhanced radiation-induced apoptosis [22].
• Induction of HSP 70 in T-cell clones with sodium arsenite had a similar protective effect against radiation-induced apoptosis [23].
• While radiation-induced apoptosis appeared most frequently at 6 h after irradiation, doxorubicin-induced apoptosis had a tendency to appear later [24].
• Loss of ceramide production confers resistance to radiation-induced apoptosis [25].
• Flow cytometric analysis further demonstrated that treatment of SCCs with ZD1839 amplified radiation-induced apoptosis [26].

Regulatory relationships of Rapop1

• These results demonstrated that PKCdelta overexpression enhanced radiation-induced apoptosis and radiosensitivity via ERK1/2 activation, thereby abolishing the radiation-induced G(2)-M arrest and finally apoptosis [27].
• CONCLUSIONS: Our data show that HSP 70 induction protects thymocytes from radiation-induced apoptosis by down-regulating p53 and bax expression [23].
• Flt3 isoforms containing ITD mutations (Flt3-ITD) induced factor-independent growth and resistance to radiation-induced apoptosis in 32D cells [28].
• Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling and annexinV-propidium iodide staining revealed the increase of radiation-induced apoptosis in the cells with inhibited NF-kappaB signaling [29].
• Bcl-XL antisense oligonucleotides coupled with antennapedia enhances radiation-induced apoptosis in pancreatic cancer [30].

Other interactions of Rapop1

• C.S-R1 and C.S-R1L were both less sensitive to radiation lymphomagenesis than BALB/c. Our study provides strong evidence for Prkdc as a candidate for Rapop1 and a susceptibility gene for radiation lymphomagenesis as well [14].
• Radiation induced apoptosis at the same levels in PRMs of p53 knockout mice and atm knockout mice as those of wild-type C3H mice; however radiation-induced apoptosis was significantly less extensive in the thymocytes of these mutant mice than in those of wild-type mice [18].
• The p53 wild type mice with a STS/A allele at the Rapop1 locus were less susceptible to both radiation- and glucocorticoid-induced apoptosis than those with homozygous BALB/cHeA alleles at this locus [31].
• DR5 knockout mice are compromised in radiation-induced apoptosis [32].
• In addition, ectopic overexpression of IRF-1 results in the activation of the endogenous Ice gene and enhances the sensitivity of cells to radiation-induced apoptosis [33].

Analytical, diagnostic and therapeutic context of Rapop1

• For those analyses, we used Rapop1 semicongenic mice heterozygous for the STS and BALB/cHeA alleles in the chromosomal segment containing Rapop1 in the BALB/cHeA background, mice bearing a p53 deficient allele in the BALB/cHeA background and the genetic crosses between these mice [31].
• Genetic dissection of susceptibility to radiation-induced apoptosis of thymocytes was performed by counting dead cells in histologically processed thymuses after 0.5 Gy of whole-body X-irradiation, using recombinant congenic (CcS/Dem) strains derived from inbred mouse strains BALB/cHeA (susceptible) and STS/A (resistant) [34].
• The length of tumor growth delay after single-dose or fractionated radiotherapy strongly correlated with the extent of radiation-induced apoptosis in the xenograft tumors as measured by terminal deoxynucleotidyl transferase-mediated nick end labeling [35].
• The unusual dose-response characteristics observed in some experimental models of radiation-induced apoptosis may require a reappraisal of standard linear quadratic and alpha/beta algorithms used to predict target tissue cytoreduction after radioimmunotherapy [36].
• MATERIALS AND METHODS: We subjected 276 second filial generation (F2) mice descended from two inbred mouse strains, radiation-induced apoptosis sensitive C57BL/6JNrs (B6) and radiation-induced apoptosis resistant C3H/HeNrs (C3H), to 2.5 Gy whole-body irradiation [37].

References