Correlation of Micronucleus and Apoptosis Assays with Reproductive Cell Death

Abend, Michael; Rhein, A; Gilbertz, Klaus-Peter; Blakely, William F.; Beuningen, D. van

doi:10.1080/09553009514550371

Cited by 62 publications

(22 citation statements)

References 32 publications

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“…These data suggest that the increased cell death by the combined treatment could be accounted for by the sum of the micronucleated and apoptotic cells in the irradiated population. This observation is in agreement with Abend et al (39), who found that for three cell lines, including HL-60, the summation of two kinds of cellular damage, micronuclei production and apoptosis, correlated well with cell clonogenic survival.…”

Section: Discussionsupporting

confidence: 82%

Enhancement of radiation response with combined Ganoderma lucidum and Duchesnea chrysantha extracts in human leukemia HL-60 cells

Kim

Jun²,

Kim³

et al. 2008

Int J Mol Med

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Abstract. We previously demonstrated that combined treatment with extracts of the medicinal mushroom Ganoderma lucidum and the herb Duchesnea chrysantha (GDE) significantly suppresses cell growth and selectively induces apoptosis in human leukemia HL-60 cells, but not in normal cells. GDE's mechanism of action and its activity against HL-60 cells suggest that it could be suitable for the combined-modality treatment of hematological malignancies. In the present study, we examined whether treatment with a combination of GDE and ionizing radiation enhances the therapeutic effect. We demonstrated that, when used in combination with radiation at a clinically relevant dose of 2 Gy, GDE further suppressed cell proliferation and induced apoptosis as well as micronuclei formation in HL-60 cells, leading to increased cell death. Furthermore, GDE pretreatment not only reduced radiation-induced G 2 /M-phase arrest, but also induced G 1 -phase arrest. These events are associated with the inhibition of cyclin-dependent kinase 1 (CDK1) phosphorylation and the dephosphorylation of retinoblastoma protein (pRB). Collectively, these data show that combined treatment with GDE and radiation enhances radiation-induced apoptosis and overall cell death. These findings may be clinically relevant and suggest a novel therapeutic strategy for increasing the efficacy of radiotherapy.

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Section: Discussionsupporting

confidence: 82%

Enhancement of radiation response with combined Ganoderma lucidum and Duchesnea chrysantha extracts in human leukemia HL-60 cells

Kim

Jun²,

Kim³

et al. 2008

Int J Mol Med

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“…p53 requirement Although HL60 cells are generally considered null for p53 (Wolf and Rotter, 1985), at least one subclone of these cells has been reported to contain p53 (Hopcia et al, 1996). Di erences in the endogenous p53 status may contribute to substantial di erences in the intrinsic radiosensitivity of several available subclones of the HL60 cells (Abend et al, 1995;Hopcia et al, 1996;Makepeace et al, 1996). We con®rmed the lack of endogenous p53 in the clone used in the present study ( Figure 6).…”

Section: Characterization Of Csa-19supporting

confidence: 59%

Csa-19, a radiation-responsive human gene, identified by an unbiased two-gel cDNA library screening method in human cancer cells

et al. 1997

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A novel polymerase chain reaction (PCR)-based method was used to identify candidate genes whose expression is altered in cancer cells by ionizing radiation. Transcriptional induction of randomly selected genes in control versus irradiated human HL60 cells was compared. Among several complementary DNA (cDNA) clones recovered by this approach, one cDNA clone (CL68-5) was downregulated in X-irradiated HL60 cells but una ected by 12-O-tetradecanoyl phorbol-13-acetate, forskolin, or cyclosporin-A. DNA sequencing of the CL68-5 cDNA revealed 100% nucleotide sequence homology to the reported human Csa-19 gene. Northern blot analysis of RNA from control and irradiated cells revealed the expression of a single 0.7-kilobase (kb) messenger RNA (mRNA) transcript. This 0.7-kb Csa-19 mRNA transcript was also expressed in a variety of human adult and corresponding fetal normal tissues. Moreover, when the e ect of X-or ®ssion neutronirradiation on Csa-19 mRNA was compared in cultured human cells di ering in p53 gene status (p537/7 versus p53+/+), downregulation of Csa-19 by X-rays or ®ssion neutrons was similar in p53-wild type and p53-null cell lines. Our results provide the ®rst known example of a radiation-responsive gene in human cancer cells whose expression is not associated with p53, adenylate cyclase or protein kinase C.

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“…Typical normal urothelial cells are shown in ( Figure 1C). Samples were scored for the presence of micronucleated ( Figure 1D) and apoptotic ( Figure 1E, F) cells measured as total cell damage (Abend et al, 1995(Abend et al, , 2000. Micronuclei appeared as green-coloured round bodies separated from the main nucleus as previously described (Belyakov et al, 1999).…”

Section: Scoring Of Micronucleated and Apoptotic Cellsmentioning

confidence: 99%

A proliferation-dependent bystander effect in primary porcine and human urothelial explants in response to targeted irradiation

Belyakov

Folkard

Mothersill³

et al. 2003

Br J Cancer

104

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The aim of this study was to test whether radiation-induced bystander effects are involved in the response of multicellular systems to targeted irradiation. A primary explant technique was used that reconstructed the in vivo microarchitecture of normal urothelium with proliferating and differentiated cells present. Sections of human and porcine ureter were cultured as explants and irradiated on day 7 when the urothelial outgrowth formed a halo around the tissue fragment. The Gray Cancer Institute charge particle microbeam facility allowed the irradiation of individual cells within the explant outgrowth with a predetermined exact number of 3 He 2+ ions (which have very similar biological effectiveness to a-particles). A total of 10 individual cell nuclei were irradiated with 10 3 He 2+ ions either on the periphery, where proliferating cells are located, or at the centre of the explant outgrowth, which consisted of terminally differentiated cells. Samples were fixed 3 days after irradiation, stained and scored. The fraction of apoptotic and micronucleated cells was measured and a significant bystander-induced damage was observed. Approximately 2000 -6000 cells could be damaged by the irradiation of a few cells initially, suggesting a cascade mechanism of cell damage induction. However, the fraction of micronucleated and apoptotic cells did not exceed 1 -2% of the total number of the cells within the explant outgrowth. It is concluded that the bystander-induced damage depends on the proliferation status of the cells and can be observed in an in vitro explant model.

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Correlation of Micronucleus and Apoptosis Assays with Reproductive Cell Death

Cited by 62 publications

References 32 publications

Enhancement of radiation response with combined Ganoderma lucidum and Duchesnea chrysantha extracts in human leukemia HL-60 cells

Enhancement of radiation response with combined Ganoderma lucidum and Duchesnea chrysantha extracts in human leukemia HL-60 cells

Csa-19, a radiation-responsive human gene, identified by an unbiased two-gel cDNA library screening method in human cancer cells

A proliferation-dependent bystander effect in primary porcine and human urothelial explants in response to targeted irradiation

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