dose fractionation

Experiments in radiation biology have found that as the absorbed dose of radiation increases, the number of cells which survive decreases. They have also found that if the radiation is fractionated into smaller doses, with one or more rest periods in between, fewer cells die. This is because of self-repair mechanisms which repair the damage to DNA{{cite web|url=http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/D/DNArepair.html|title=DNA repair|author=John Kimball|date=8 April 2012|accessdate=2012-06-24|archive-date=2018-02-12|archive-url=https://web.archive.org/web/20180212073520/http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/D/DNArepair.html|url-status=dead}}{{cite web|url=http://www.benbest.com/lifeext/aging.html#dna|title=Mechanisms of Aging|author=Ben Best|accessdate=2012-06-24}} and other biomolecules such as proteins. These mechanisms can be over expressed in cancer cells, so caution should be used in using results for a cancer cell line to make predictions for healthy cells if the cancer cell line is known to be resistant to cytotoxic drugs such as cisplatin.{{cite journal |last1=Niu |first1=Nifang |last2=Wang |first2=Liewei |title=human cell line models to predict clinical response to anticancer drugs |journal=Pharmacogenomics |date=March 2015 |volume=16 |issue=3 |pages=273–285 |doi=10.2217/pgs.14.170 |pmc=4358765 |pmid=25712190}}{{cite journal |last1=Gillet |first1=J.-P. |last2=Calcagno |first2=A. M. |last3=Varma |first3=S. |last4=Marino |first4=M. |last5=Green |first5=L. J. |last6=Vora |first6=M. I. |last7=Patel |first7=C. |last8=Orina |first8=J. N. |last9=Eliseeva |first9=T. A. |last10=Singal |first10=V. |last11=Padmanabhan |first11=R. |last12=Davidson |first12=B. |last13=Ganapathi |first13=R. |last14=Sood |first14=A. K. |last15=Rueda |first15=B. R. |last16=Ambudkar |first16=S. V. |last17=Gottesman |first17=M. M. |title=Redefining the relevance of established cancer cell lines to the study of mechanisms of clinical anti-cancer drug resistance |journal=Proceedings of the National Academy of Sciences |date=8 November 2011 |volume=108 |issue=46 |pages=18708–18713 |doi=10.1073/pnas.1111840108 |pmc=3219108|bibcode=2011PNAS..10818708G |pmid=22068913|doi-access=free }} The DNA self repair processes in some organisms is exceptionally good; for instance, the bacterium Deinococcus radiodurans can tolerate a 15 000 Gy (1.5 MRad) dose.{{cite book |last1=Bakermans |first1=Corien |title=Microbial Evolution under Extreme Conditions |date=2015 |publisher=Walter de Gruyter |location=Berlin |isbn=9783110340716 |page=154 |url=https://books.google.com/books?id=V_teCAAAQBAJ&pg=PA154 |language=en}}

File:Effectofselfrepair.svg to cause cell death. The blue line is for cells which were not given a chance to recover; the red line is for cells which were allowed to stand for a time and recover.]]

In the graph to the right, called a cell survival curve, the dose vs. surviving fraction have been drawn for a hypothetical group of cells with and without a rest time for the cells to recover. Other than the recovery time partway through the irradiation, the cells would have been treated identically.

The human body contains many types of cells, and the human can be killed by the loss of a single type of cell in a vital organ. For many short-term radiation deaths due to what is commonly known as radiation sickness (3 to 30 days after exposure), it is the loss of bone marrow cells (which produce blood cells), and the loss of other cells in the wall of the intestines, that is fatal.{{cite web |title=Acute Radiation Syndrome: A Fact Sheet for Physicians |url=https://www.cdc.gov/nceh/radiation/emergencies/arsphysicianfactsheet.htm |publisher=Centers for Disease Control and Prevention |accessdate=7 November 2019 |language=en-us |date=4 April 2018}}

Fractionation effects are utilised in the treatment of cancer with radiation therapy. When the total dose of radiation is divided into several, smaller doses over a period of several days, there are fewer toxic effects on healthy cells. This maximizes the effect of radiation on cancer and minimizes the negative side effects. A typical fractionation scheme divides the dose into 30 units delivered every weekday over six weeks.{{cite web |title=Radiotherapy dose fractionation, second edition |url=https://www.rcr.ac.uk/publication/radiotherapy-dose-fractionation-second-edition |website=The Royal College of Radiologists |language=en |date=2016}}{{cite book |last1=Jones |first1=Bleddyn |last2=Morgan |first2=David AL |editor1-last=Dale |editor1-first=Roger G. |editor2-last=Jones |editor2-first=Bleddyn |title=Radiobiological modelling in radiation oncology |date=2007 |publisher=British Institute of Radiology |location=London |isbn=9780905749600 |chapter=Radiotherapy fractionation|doi=10.1259/9780905749839.chapter04}}

Hypofractionation is a treatment regimen that delivers higher doses of radiation in fewer visits. The logic behind this treatment is that applying greater amounts of radiation works to lower the effects of accelerated tumor growth that typically occurs during the later stages of radiotherapy.Pollack, Alan, and Mansoor Ahmed. Hypofractionation: Scientific Concepts and Clinical Experiences. 1st. Ellicot City: LimiText Publishing, 2011

Hyperfractionation is dividing the same total dose into more deliveries. Treatments are given more than once a day. Hyperfractionated radiation therapy is given over the same period of time (days or weeks) as standard radiation therapy.{{cite web |title=Hyperfractionated radiation therapy |url=https://www.cancer.gov/publications/dictionaries/cancer-terms/def/hyperfractionated-radiation-therapy |website=NCI Dictionary of Cancer Terms |publisher=National Cancer Institute |accessdate=9 June 2018 |language=en}}

Accelerated fractionation (two deliveries per day and/or deliveries on weekends as well) has also been investigated.{{cite web |title=Accelerated-fraction radiation therapy|url=https://www.cancer.gov/publications/dictionaries/cancer-terms/def/accelerated-fraction-radiation-therapy |website=NCI Dictionary of Cancer Terms |publisher=National Cancer Institute |accessdate=9 June 2018 |language=en}}

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Category:Cell biology

Category:Radiation

Category:DNA