The effect of dose fractionation on γ-radiation induced mutations in mammalian cells

Abstract γ-Radiation is a potent inducer of apoptosis. There are multiple pathways regulating DNA damage-induced apoptosis, and we set out to identify novel mechanisms regulating γ-radiation–induced apoptosis in hematopoietic cells. In this report, we present data implicating the cyclin B1 protein as a regulator of apoptotic fate following DNA damage. Cyclin B1 is the regulatory subunit of the cdc2 serine/threonine kinase, and accumulation of cyclin B1 in late G2 phase of the cell cycle is a prerequisite for mitotic initiation in mammalian cells. We find that abundance of the cyclin B1 protein rapidly increases in several mouse and human hematopoietic cells (Ramos, DP16, HL60, thymocytes) undergoing γ-radiation–induced apoptosis. Cyclin B1 accumulation occurs in all phases of the cell cycle. Antisense inhibition of cyclin B1 accumulation decreases apoptosis, and ectopic cyclin B1 expression is sufficient to induce apoptosis. These observations are consistent with the idea that cyclin B1 is both necessary and sufficient for γ-radiation-induced apoptosis.

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Mutational Specificity of γ-Radiation-Induced Guanine−Thymine and Thymine−Guanine Intrastrand Cross-Links in Mammalian Cells and Translesion Synthesis Past the Guanine−Thymine Lesion by Human DNA Polymerase η†

Biochemistry ◽

10.1021/bi800529f ◽

2008 ◽

Vol 47 (31) ◽

pp. 8070-8079 ◽

Cited By ~ 43

Author(s):

Laureen C. Colis ◽

Paromita Raychaudhury ◽

Ashis K. Basu

Keyword(s):

Dna Polymerase ◽

Mammalian Cells ◽

Translesion Synthesis ◽

Γ Radiation ◽

Human Dna ◽

Mutational Specificity ◽

Radiation Induced ◽

Cross Links

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Abundance of cyclin B1 regulates γ-radiation–induced apoptosis

Blood ◽

10.1182/blood.v95.8.2645.008k18_2645_2650 ◽

2000 ◽

Vol 95 (8) ◽

pp. 2645-2650 ◽

Cited By ~ 5

Author(s):

Lisa A. Porter ◽

Gurmit Singh ◽

Jonathan M. Lee

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Mammalian Cells ◽

Hematopoietic Cells ◽

Cyclin B1 ◽

Regulatory Subunit ◽

Potent Inducer ◽

Γ Radiation ◽

Radiation Induced ◽

Induced Apoptosis

γ-Radiation is a potent inducer of apoptosis. There are multiple pathways regulating DNA damage-induced apoptosis, and we set out to identify novel mechanisms regulating γ-radiation–induced apoptosis in hematopoietic cells. In this report, we present data implicating the cyclin B1 protein as a regulator of apoptotic fate following DNA damage. Cyclin B1 is the regulatory subunit of the cdc2 serine/threonine kinase, and accumulation of cyclin B1 in late G2 phase of the cell cycle is a prerequisite for mitotic initiation in mammalian cells. We find that abundance of the cyclin B1 protein rapidly increases in several mouse and human hematopoietic cells (Ramos, DP16, HL60, thymocytes) undergoing γ-radiation–induced apoptosis. Cyclin B1 accumulation occurs in all phases of the cell cycle. Antisense inhibition of cyclin B1 accumulation decreases apoptosis, and ectopic cyclin B1 expression is sufficient to induce apoptosis. These observations are consistent with the idea that cyclin B1 is both necessary and sufficient for γ-radiation-induced apoptosis.

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DNA sequence determination of γ-radiation-induced mutations of the hamster aprt locus

Mutation Research Letters ◽

10.1016/0165-7992(89)90004-3 ◽

1989 ◽

Vol 227 (2) ◽

pp. 97-102 ◽

Cited By ~ 41

Author(s):

Carol Miles ◽

Mark Meuth

Keyword(s):

Dna Sequence ◽

Induced Mutations ◽

Sequence Determination ◽

Γ Radiation ◽

Radiation Induced

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Involvement of the MKK6-p38γ Cascade in γ-Radiation-Induced Cell Cycle Arrest

Molecular and Cellular Biology ◽

10.1128/mcb.20.13.4543-4552.2000 ◽

2000 ◽

Vol 20 (13) ◽

pp. 4543-4552 ◽

Cited By ~ 190

Author(s):

Xiaofei Wang ◽

Clare H. McGowan ◽

Ming Zhao ◽

Liusheng He ◽

Jocelyn S. Downey ◽

...

Keyword(s):

Mammalian Cells ◽

Dominant Negative ◽

Γ Irradiation ◽

Γ Radiation ◽

Cycle Arrest ◽

Protein Map ◽

Mitogen Activated Protein ◽

Radiation Induced ◽

High Degree ◽

Degree Of Similarity

ABSTRACT The p38 group of kinases belongs to the mitogen-activated protein (MAP) kinase superfamily with structural and functional characteristics distinguishable from those of the ERK, JNK (SAPK), and BMK (ERK5) kinases. Although there is a high degree of similarity among members of the p38 group in terms of structure and activation, each member appears to have a unique function. Here we show that activation of p38γ (also known as ERK6 or SAPK3), but not the other p38 isoforms, is required for γ-irradiation-induced G2arrest. Activation of the MKK6-p38γ cascade is sufficient to induce G2 arrest in cells, and expression of dominant negative alleles of MKK6 or p38γ allows cells to escape the DNA damage-induce G2 delay. Activation of p38γ is dependent on ATM and leads to activation of Cds1 (also known as Chk2). These data suggest a model in which activation of ATM by γ irradiation leads to the activation of MKK6, p38γ, and Cds1 and that activation of both MKK6 and p38γ is essential for the proper regulation of the G2checkpoint in mammalian cells.

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MOLECULAR GENETIC ANALYSIS OF THE DILUTE-SHORT EAR (d-se) REGION OF THE MOUSE

Genetics ◽

10.1093/genetics/112.2.321 ◽

1986 ◽

Vol 112 (2) ◽

pp. 321-342

Author(s):

Eugene M Rinchik ◽

Liane B Russell ◽

Neal G Copeland ◽

Nancy A Jenkins

Keyword(s):

Physical Map ◽

Leukemia Virus ◽

Molecular Genetic ◽

Break Point ◽

Virus Genome ◽

Molecular Genetic Analysis ◽

Chromosome 9 ◽

Genetic Complementation ◽

Induced Mutations ◽

Radiation Induced

ABSTRACT Genes of the dilute-short ear (d-se) region of mouse chromosome 9 comprise an array of loci important to the normal development of the animal. Over 200 spontaneous, chemically induced and radiation-induced mutations at these loci have been identified, making it one of the most genetically well-characterized regions of the mouse. Molecular analysis of this region has recently become feasible by the identification of a dilute mutation that was induced by integration of an ecotropic murine leukemia virus genome. Several unique sequence cellular DNA probes flanking this provirus have now been identified and used to investigate the organization of wild-type chromosomes and chromosomes with radiation-induced d-se region mutations. As expected, several of these mutations are associated with deletions, and, in general, the molecular and genetic complementation maps of these mutants are concordant. Furthermore, a deletion break-point fusion fragment has been identified and has been used to orient the physical map of the d-se region with respect to the genetic complementation map. These experiments provide important initial steps for analyzing this developmentally important region at the molecular level, as well as for studying in detail how a diverse group of mutagens acts on the mammalian germline.

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A review on radiation induced nausea and vomiting: “Current management strategies and prominence of radio sensitizers”

Journal of Oncology Pharmacy Practice ◽

10.1177/10781552211011539 ◽

2021 ◽

pp. 107815522110115

Author(s):

Meenu Vijayan ◽

Sherin Joseph ◽

Emmanuel James ◽

Debnarayan Dutta

Keyword(s):

Radiation Therapy ◽

Cell Damage ◽

Genetic Material ◽

High Energy ◽

Concurrent Chemotherapy ◽

Nausea And Vomiting ◽

Dose Fractionation ◽

Psychological State ◽

Related Factors ◽

Radiation Induced

Radiations dissipated are high energy waves used mostly as treatment intervention in controlling the unwanted multiplication of cell. About 60%–65% of cancer treatment requires radiation therapy and 40%–80% of radiation therapy causes RINV which are true troublemakers. Radiation therapy (RT) is targeted therapy mostly used to treat early stages of tumour and prevent their reoccurrence. They mainly destroy the genetic material (DNA) of cancerous cells to avoid their unwanted growth and division. The RINV affects the management and quality of life of patients which further reduces the patient outcome. RINV depends on RT related factors (dose, fractionation, irradiation volume, RT techniques) and patient related factors like (gender, health conditions, age, concurrent chemotherapy, psychological state, and tumour stage). RT is an active area of research and there is only limited progress in tackling the RINV crisis. Advanced technological methods are adopted that led to better understanding of total lethal doses. Radiation therapy also affects the immunity system that leads to radiation induced immune responses and inflammation. Radio sensitizers are used to sensitize the tumour cells to radiations that further prevent the normal cell damage from radiation exposure. There is a need for future studies and researches to re-evaluate the data available from previous trials in RINV to make better effective antiemetic regimen. The article focuses on radiation therapy induced nausea and vomiting along with their mechanism of action and treatment strategies in order to have a remarkable patient care.

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