The main forms of cell death postirradiation are mitotic death and interphase death. The latter is also called apoptosis (programed cell death). In this context, necrosis occurs mainly after circulation failure and oxygen starvation. Apoptosis is most frequent in hematological cells, and rare in fibroblasts. For most monolayer culture cells, postirradiation death is mitotic (failure to complete mitosis). The cells may remain static nonproliferating or they may eventually lyse. The G2/M block affects viable cells as well as those due to die. This block position was measured by Stefan after only 9 rads (0.09 Gy), obviously most of the cells were survivors. It is only if they fail to repair all of their double-strand breaks before mitosis that they die (a mitotic death).

I think Dr Lange gave a thorough answer.

In my opinion Catastrophe mitotic is the main mechanism of cell death. It would be of interest to have a look to this paper Oncogene (2004) 23, 6548–6558. doi:10.1038/sj.onc.1207873 Published online 28 June 2004

thanks to all, i have gone through the paper earlier, but the question is what about apoptotic death after release of G2/M phase arrest. Hoe we can segregate that cells which were going to mitotic death drive to them into apoptotic death or vice versa, what about senescence after irradiation and continuous arrest in any phase of cell cycle?

http://ar.iiarjournals.org/content/24/2B/555.full.pdf

Ionizing Radiation Inhibits the PLK Cell Cycle Gene in a G2 Checkpoint-dependent Manner

ANNE HANSEN, REEÅSE BRATLAN, KIRSTI SOLBERG LANDSVERK and ØYSTEIN FODSTAD1

Departments of Tumor Biology, Oncology and Biophysics, The Norwegian Radium Hospital, 0310 Oslo, Norway

http://clincancerres.aacrjournals.org/content/6/9/3756.full.pdf

Early Caspase Activation in Leukemic Cells Subject to Etoposideinduced G2

-M Arrest: Evidence of Commitment to Apoptosis

Rather Than Mitotic Cell Death

1

Robert J. Sleiman and Bernard W. Stewart

2

Children’s Cancer Institute Australia, Sydney Children’s Hospital,

Sydney 2031 [R. J. S., B. W. S.], and School of Paediatrics,

University of New South Wales, Sydney 2052 [B. W. S.], Australia

Hey, dmitri thanks for your attention but dont spoil the issues, give real comments

Hey, Krishnanang . The link between question and answers is a real comment.

Cell cycle specific induction of apoptosis and necrosis by paclitaxel in the leukemic U937 cells

Pei-Chin Liao, Chien-Hui Lieu,

Faculty of Biotechnology and Laboratory Science in Medicine/Institute of Biotechnology in Medicine, National Yang-Ming University, Taipei, Taiwan 112, Republic of China

Abstract

Induction of cell apoptosis and necrosis by paclitaxel was investigated in human leukemic U937 cells. To explore whether paclitaxel induces both apoptosis and necrosis in different cell cycle stages, we synchronized the cells in G1, S and G2/M stages by counterflow centrifugal elutriation (CCE). The Annexin V and PI analysis revealed that, after paclitaxel treatment, the cells in G1 and S stages died predominantly through apoptosis, whereas G2/M-stage cells died through both apoptosis and necrosis. These phenomena were verified by a trypan blue exclusion assay and by detection of the release of lactose dehydrogenase (LDH). Paclitaxel treatment significantly decreased viability in G2/M cells and led these cells to release more LDH than other cells. These treated cells also released certain substances that inhibited cell growth. These results strongly suggest that the cell membrane of the treated G2/M-cells is disrupted, leading to the leakage of LDH and cell growth inhibitory substances out of cell. Furthermore, the typical events of apoptosis, such as the release of cytochrome c and the decrease of mitochondria membrane potential, occur primarily in S stage rather than in the G2/M stages. These results suggest that paclitaxel induces typical apoptosis in the G1- and S- cells, but it induces both apoptosis and necrosis in G2/M-phase cells.

It should be clear. Toxicity and inflammation coming only after cell necrosis but never after apoptosis.

U are true Dr Jerry, nice comments thats called to be clear comment, add up more

Many cells goes for death even at low dose for example in cGy. Therefore, dissecting out the modalities and reprogramming the one mode into other is a challenging task..

The mode of death selected by the cells in a solid tumor population depends upon the heterogenity of the cells in the tumor samples( eg grade Iv Glioma cells are know to be very resistant to Radiation induced death). Therefore currently we know for sure that there are different types of cells in the same soild tumor which will behave differentially after challenging them with a particular therapeutic dose of ionizing radiation. recent reports also suggest that Tumor inducing sub population of cancer stem cells are the most resistant variety of cells. the resistance is due to alternative DNa repair capacity of cancer cells. So overall we can conclude that radiation resistant cells survive the insult or few of them die via necrosis and the rest of the cells at various stages of cell- cycle undergoes DNA fragmentation and Apoptosis.

Dr Banerjee what u have concluded is cell type specific or general because many times cell goes for arrest and they don't go for death at all, what about that?

As I noted several days ago, G2/M block affects BOTH cells that will survive and those doomed to die. Steffan showed that this occurs to most of the cell population after 9 cGy (rads), a dose likely to leave most cells as survivors.The mode of death of the decedants in most often mitotic death for solid tumor cells (and most normal tissues), with the exception of hematological cells and hematological cancers, which preferentially undergo apoptosis. Apoptosis in fibroblasts, if and when it occurs, happens after mitotic death. A cell can be sterilized, i.e., lose its reproductive integrity, and still remain capable of differentiation or physical survival. This is quite different from apoptosis, which is a mechanism for cell removal to prevent necrosis.

As I said earlier there cannot be a general thumb rule of how the cells are dying in general after radaition treatment. In a solid tumor there are different categories of cells which respond differentially to the ionizing radiation depending on their sub-genotype and class. The resistant, tumor inducing stem cell type after undergoing the insult--- quickly heal their DNA and divide(transitory arrest), there are others who do not die but they remain arrested and stop cycling or senesce and die later via apoptosis, there are others which do not repair their DSBs and get selected for apoptosis. Therefore in the same tumnor sample a varity of mechanism is chosen and different repair pathways are chosen as well. So simple thumb rule death processes must not be the asnwer..

excellent response, thanks to Dr Lange for realistic answer , but if we say in a group of cells few goes for death through apoptosis, necrosis, mitotic catastrophe and autophagic feature , then how this can be explained?

How insult dependent death of different types occurs and how we can modulate one into another is still not resolving?

nice comments from Dr Banergee and Dr Battista

Add up more regarding normal versus tumor cell response in this chapter

"Therefore currently we know for sure that there are different types of cells in the same soild tumor which will behave differentially after challenging them with a particular therapeutic dose of ionizing radiation."

Hematological cells - depend on doses - may die through apoptosis or through necrosis. Necrosis/apoptosis - both Programmed Cell Death. And pathways quite similar.

I am not giving an answer but raising a question relevant to the original question.

This discussion was made 6 years ago. Now, in 2018 my group is revisiting the same question. I am a medical physicist and in the traditional radiobiology class, we learn the L-Q model, which quantifies the radiation-induced cell death by simply the number/or the probability of double-strand breaks. How does the model fit the reality when the apoptosis plays significant role in the radiation response of the cells. The L-Q model is the basis of all our clinical practices currently.