X-Ray-Induced Cell Death: Apoptosis and Necrosis

Nakano, Hisako; Shinohara, Kunio

doi:10.2307/3578561

Cited by 55 publications

(29 citation statements)

References 21 publications

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“…These long DNA molecules could be derived from necrosis instead of apoptosis. It has been reported that cell death associated with tissue necrosis may generate longer DNA fragments in addition to the typical oligonucleosomal DNA fragments (42,43). For future studies, it would be interesting to study the DNA methylation profile of these longer DNA molecules to see if they bear resemblances to that expected for the liver.…”

Section: Discussionmentioning

confidence: 99%

Lengthening and shortening of plasma DNA in hepatocellular carcinoma patients

Jiang

Chan

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

599

522

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The analysis of tumor-derived circulating cell-free DNA opens up new possibilities for performing liquid biopsies for the assessment of solid tumors. Although its clinical potential has been increasingly recognized, many aspects of the biological characteristics of tumor-derived cell-free DNA remain unclear. With respect to the size profile of such plasma DNA molecules, a number of studies reported the finding of increased integrity of tumor-derived plasma DNA, whereas others found evidence to suggest that plasma DNA molecules released by tumors might be shorter. Here, we performed a detailed analysis of the size profiles of plasma DNA in 90 patients with hepatocellular carcinoma, 67 with chronic hepatitis B, 36 with hepatitis B-associated cirrhosis, and 32 healthy controls. We used massively parallel sequencing to achieve plasma DNA size measurement at single-base resolution and in a genome-wide manner. Tumor-derived plasma DNA molecules were further identified with the use of chromosome arm-level z-score analysis (CAZA), which facilitated the studying of their specific size profiles. We showed that populations of aberrantly short and long DNA molecules existed in the plasma of patients with hepatocellular carcinoma. The short ones preferentially carried the tumor-associated copy number aberrations. We further showed that there were elevated amounts of plasma mitochondrial DNA in the plasma of hepatocellular carcinoma patients. Such molecules were much shorter than the nuclear DNA in plasma. These results have improved our understanding of the size profile of tumor-derived circulating cell-free DNA and might further enhance our ability to use plasma DNA as a molecular diagnostic tool.tumor markers | circulating tumor DNA | liquid biopsy | massively parallel sequencing | mitochondrial DNA A nalysis of circulating cell-free DNA has been increasingly used for the detection and monitoring of cancers (1-5). Different cancer-associated molecular characteristics, including copy number aberrations (6-9), methylation changes (10-13), single-nucleotide mutations (6, 14-17), cancer-derived viral sequences (18,19), and chromosomal rearrangements (20, 21), can be detected in the plasma of patients with various types of cancers. Despite the rapid expansion of clinical applications, many fundamental molecular characteristics of circulating DNA in cancer patients remain unclear. In particular, previous studies on the size of circulating DNA in cancer patients gave inconsistent results. Studies have demonstrated that the overall integrity of circulating DNA would increase in cancer patients compared with subjects without a malignant condition (22-25). Using PCR with different amplicon sizes, it was shown that the proportion of longer DNA would be higher in cancer patients. This aberration in DNA integrity was shown to be reversible after treatment, and the persistence of such changes was associated with poor prognosis (22, 26). On the other hand, there is also seemingly contradictory evidence that circulating DNA derived from t...

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Section: Discussionmentioning

confidence: 99%

Lengthening and shortening of plasma DNA in hepatocellular carcinoma patients

Jiang

Chan

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

599

522

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“…MOLT-4 cells are derived from a human T-cell leukemia, are highly radiosensitive, and die by apoptosis after X-irradiation or hyperthermia (Han et al 1974;Akagi et al 1993;Shinohara and Nakano 1993;Nakano and Shinohara 1994;Nakano et al 1997). They accumulate p53 protein in response to various external stresses such as ionizing radiation or heat (Nakano et al 1997;Inanami et al 1999;Nakano and Shinohara 1999;Zhao et al 1999;Enomoto et al 2000).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the relative contribution of p53-mediated pathway in X-ray-induced apoptosis in human leukemic MOLT-4 cells by transfection with a mutant p53 gene at different expression levels

Nakano

Kohara

Shinohara

2001

Cell and Tissue Research

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There are several pathways leading to apoptosis. It is not clear whether cells choose one of them or use multiple processes when they commit to apoptosis. MOLT-4 cells undergo apoptosis after X-irradiation through the p53-dependent pathway and/or ceramide signal. To evaluate the relative contribution of these pathways, we studied effects of the expression of various levels of transfected murine mutant p53 cDNA (TGC-->CGC of codon 173, corresponding to codonl76 in human p53) on the induction of apoptosis in X-irradiated or heated MOLT-4 cells. When survival was determined by the dye-exclusion test at 24 h after irradiation, the percentage of X-ray- or heat-induced dead cells was markedly decreased, depending on the expression level of mutant p53 protein in transfected clones. The appearance of apoptotic cells as determined by morphological changes was also decreased. These inhibitions were almost complete at 24 h after irradiation with X-rays in the case of the highest-expressing clone. p21 WAF1 protein was increased in MOLT-4 cells after X-irradiation, but not in the transfectant. These results suggest that murine mutant p53 protein has a dominant-negative effect against normal p53 in MOLT-4, and that the X-ray-induced apoptosis in MOLT-4 is fully p53-dependent.

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“…Living cells can actively react to the X-ray induced damage by, e.g., the start of apoptosis [111]. However, for the exposure to radiation doses much lower than the doses applied here, these effects have been shown to occur on time scales of several hours [111], which is long compared to one measurement (well beyond one hour of total scan time). Fig.…”

Section: Radiation Damagementioning

confidence: 99%

“…However, the radiation can also affect other biological molecules in the cell like for instance membrane lipids, which might lead to a disturbance of the membrane function and a loss of compartmentalization [104]. The lethality of mammalian cells upon irradiation has been addressed in various studies [108][109][110][111][112][113]. In most mammalian cell populations, an exposure to a dose of 10 Gy X-rays causes more than 90% cell killing [107].…”

Section: Radiation Damage and Dosementioning

confidence: 99%

Scanning X-ray nano-diffraction on eukaryotic cells

Weinhausen¹

2014

Göttingen Series in X-Ray Physics

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X-Ray-Induced Cell Death: Apoptosis and Necrosis

Cited by 55 publications

References 21 publications

Lengthening and shortening of plasma DNA in hepatocellular carcinoma patients

Lengthening and shortening of plasma DNA in hepatocellular carcinoma patients

Evaluation of the relative contribution of p53-mediated pathway in X-ray-induced apoptosis in human leukemic MOLT-4 cells by transfection with a mutant p53 gene at different expression levels

Scanning X-ray nano-diffraction on eukaryotic cells

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