Biological effects of radiation

radiation effects on human

1. BIOLOGICAL EFFECTS OF RADIATION SABARI KUMAR P M.Sc. RADIATION PHYSICS

2. Needful definitions LET: (Linear Energy Transfer) The energy released per micron medium along the track of any ionizing particle LET  Q 2 /V 2 Slow moving and high charged particle  High LET( KeV / μ m) Fast moving and low charged particle  Low LET( KeV / μ m) Particle Charge Energy LET (keV/μm) Proton +1 Small 92 Proton +1 2MeV 16 Alpha +2 Small 260 Alpha +2 5MeV 95

3. Needful definitions RBE: (Relative Biological Effectiveness) It is the ratio of the 250KV X ray dose that produces specific biological effect to the test dose of any radiation that produces the same effect. It is related to LET RBE = 250 KV X ray dose/Tested dose of any radiation For Ex. RBE of 3 means, 3 Gy of standard radiation is needed to achieve the same cell kill as 1 Gy of test radiation Overkill effect : A single particle deposits much more energy than is required to kill a cell. Therefore, it kills less cells per absorbed dose. • OER strictly decreases as LET increases. LET<1 keV / μ m: OER=2.5–3.5 LET>100 keV / μ m: OER=1.0

4. Relation: As LET increases, RBE increases until it reaches a peak at 100 keV / μm . Decreased repair due to high density of ionizations. Increased direct action, less oxygen dependent. 100 keV / μm corresponds to one ionization per 2 nm, which is the diameter of a DNA strand, and is considered the optimal LET for cell killing . The biological effect is directly proportional to LET of radiation

5. Introduction - cell Cell is the structural and functional unit of all living organisms Cells are generally classified into two types: Somatic cells Germ cells Cell doesn’t grow indefinitely in size, instead at a certain time, it goes to divide and produces two daughter cells. Two types of cell division may be mitotic or Meiotic Germ cells are formed by Meiosis where as somatic cells are formed through mitosis division cell exhibits two phases in its life time: Inter-phase Mitosis phase

6. Cell Structure

7. CELL CYCLE Mitotic Phase is divided into 4 phases such as: Prophase Metaphase Anaphase Telophase Inter phase is the longest phase & classified into 4 stages: G1 Phase: Divisible cell growth S Phase : Protein Synthesis and DNA duplication G2 Phase: Organelles doubles and prepares cell to division G0 Phase: Delays cellular activities in case of difficulties during developing stages The Effects of radiation on cell is majorly depends on which phase of cell. Early G2 and M stages are most radio-sensitive where as G1 and S phases are radio-resistive.

8. The effect of radiation on cell causes various effects such as Cell may apoptotic (loss of proliferative capacity) mitotic death cell may survive ( Retain of reproductive capacity) DNA resides inside the cell nucleus, is the principle target for biological effects of radiation DNA is a large molecule with well known double helix structure, consists of two strands, held together by hydrogen bonds between the bases Effects of Radiation on Cell

9. Effects of Radiation on Cell

10. When DNA is damaged by radiation, basic function of cell is altered results, death of cell Abnormal modification of cell function. Irradiation can results various types of damages in which part of DNA is affected by radiation Strand breaks Alteration to bases Destruction of sugars Cross links and formation of dimmer Radiation have direct or indirect effects of DNA molecules

11. Direct Effects : Interaction of ionizing radiation directly with DNA is named as direct effect. Atoms in DNA may ionized or excited which leads to biological change. When DNA directly affected by radiation, energy absorbed by DNA undergoes to Strand breaks Direct Effect is proportional to LET of Radiation. A quarter to a third of the damage produced in cellular macro-molecules by radiation is due to its direct effect.

12. Indirect Effects : Interaction of ionizing radiation happens with other molecules or atoms rather than DNA is named as indirect effect. Most Probable Phenomena due to 70% of water composition of human body Radiation interacts water molecules results free radical generation

13. Indirect Effects: Due to short life span (10 -10 sec), combines with O 2 and forms H 2 O 2 and HO 2 with life time of 10 -5 sec Those can’t move due to little dense, prevents nutrition of neighbouring cells by oxidization Finally results cell death through nutritive deficiency or isolation of these cells from other tissues Two third of the damages caused by in this effect.

14. Molecular Level effects Strand Breaks (Single or Double) Breaks of Phosphate di -ester bond or deoxyribose . Single Strand Breaks (SSB) are little biological consequence where as Double Strand Breaks (DSB) results cell killing or Carcinogenesis or Mutation As X ray dose of 1 – 1.5 Gy produces about 1000 SSBs and 50 – 100 DSBs SSBs are directly proportional to dose (0.2 – 60000 Gy ) When come to DSBs, the relation with dose is dispute (linear quadratic relation)

15. Alteration of Bases Bases can be partially destroyed or chemically modified Two or three of base alterations can be seen for 10 SSB Destruction of Sugars Alteration of deoxy -ribose are rarer and not well understood. Only 0.2 to 0.3 alterations of sugars per 10SSBs have identified Cross links and Formation of dimmers

16. Cellular Level Effects Inhibition of division - cell division is inhibited/delayed Chromosome aberrations - structure or number of chromosome altered Gene mutation - DNA sequence of A,T,G,C bases altered Cell Killing/cell death - cell stops dividing or functioning

17. Chromosomal Aberrations: When cells are irradiated with X rays, DBSs are produced in chromosomes and broken ends appear to be sticky and can rejoin with any other sticky end in variety of ways Breaks may restitute Breaks may fails to rejoin and give rise to an aberration (deletion of next mitosis) Broken ends may re-assort and rejoin with other ends and rise to distorted chromosomes follows next mitosis Usually aberrations seen at interphase and lethal to cells in three different ways: Di-centric Ring Anaphase Bridge

18. Types of Effects The effects of radiation in human body are classified into two depends on which cells are damaged. Somatic effects – Arises from damage to somatic cells Majorly depends on dose, fractionation & volume irradiated affect only exposed individual Genetic effects – Arises from damage of reproductive cells and manifest in the progeny of exposed person These effects may be either Early or Late May appear immediately (few hours to weeks) after exposure or appear much later (years or decades) after exposure

19. Early effects: Acute exposures causes early effects Usually found in high proliferative cells like bone marrow epidermis Starts with vascular changes, clinically visible as erythema . Eventually, healing occurs based on surviving stem cells After irradiation, each of he cells in a given tissue has a certain probability of being killed and this probability increases with dose.

20. THRESHOLD DOSE SYMPTOMS 1 Gy N ausea V omiting D iarrhea Fatigue Headache Lack of appetite Time of appearance & severity Depends on dose. Within 1-24 hours Consequences Person recovers within 1-2 days Radiation Sickness

21. THRESHOLD DOSE SYMPTOMS 3 to 5 Gy Anemia Infection Fever Hemorrhage Time of appearance & severity Depends on dose. Within 1 to 2 months Consequences LD 50/60 Time of death after exposure 30 – 60 days Bone Marrow Syndrome

22. THRESHOLD DOSE SYMPTOMS 5 to 15 Gy Damage to Small Intestine Poor Food intake Less nutrition absorption Diarrhea, Ulceration & Low BP Circulatory collapse Consequences Death between 1 – 2 weeks Gastro Intestine Syndrome

23. THRESHOLD DOSE SYMPTOMS >15 Gy Coma Tremors Ataxia Convulsions Delirium Time of appearance & severity within few hours dose dependent Consequences Death in <5 days dose dependent CNS Syndrome

24. Dose Range Effect <0.1Gy Chromosomal Aberrations detectable <0.5GY Transient reduction in WBC Temporary Sterility in males <1.0Gy NVD Syndrome <3.0Gy Damage of BM, Lymph nodes , Spleen; Death in 4 to 8 weeks (10%) <5.0Gy LD50/60 <15.0Gy Gastro-intestinal syndrome death in 1-2 weeks (100%) >15.0Gy CNS syndrome death in few hours to days Early Somatic effects due to acute whole body exposures due to Low LET

25. Dose Range Region Effect 0.1Gy Testes Temporary Sterility 3.5 – 6 Gy Testes Permanent Sterility 1.5-2.0Gy Ovaries Temporary Sterility 2.5-6.0Gy Ovaries Permanent Sterility 0.5Gy Eye Cataract (After few years) 6.0Gy Skin Permanent Epilation 10-15Gy Skin Death of Tissue Somatic effects due to acute whole body exposures due to Low LET When compared to whole body exposure, partial body exposure will not be life threatening , however it can produce certain serious local effects These local effects are depends on dose rate and period of exposure All the early somatic effects do have a threshold dose limit.

26. Late Effects: Exposed to low levels of radiation over a prolonged period may lead to late effects These effects may found in all organs Late radiation effects are irreversible and progressive with increasing severity occurring with longer follow up times Progression rate is depends on dose and dose rate Ex: Tolerance dose for eye are reported in the range of 4-5Gy for fractionated exposure but 1Gy for single exposure

27. Hereditary Effects: Consequence of mutations induced in germ cells due to exposures results adverse health effects in the descendants To estimate the risk of radiation induced hereditary diseases in the human, two quantities are required: Base line Mutation rate for human Doubling dose- the dose required to double the spontaneous mutation rate Hereditary consequences of a given dose can be reduced greatly if a time interval is allowed between irradiation and conception ICRP estimates that the hereditary risk of radiation is about 0.2%/ Sv in general public and 0.1%/ Sv for workers

28. Deterministic Effects: Deterministic effects due to the killing/ malfunction of cells following higher doses All these effects will definitely appear in the exposed individual, if person exposed to threshold doses Severity of symptoms with doses Can completely avoided by limiting the dose well below the threshold levels Ex : All whole Body Syndromes Partial Body effects dose Severity of effect threshold

29. Stochastic Effects: These are statistical in nature Any dose, however small, is effective for a certain level of risk for induction of these effects The risk increases as the dose increases As such no threshold dose for these effects Risk of occurrence can’t be completely avoided but can minimized to an acceptable level Ex : Cancer , Hereditary effects But, the human beings exposed in high background radiation areas to doses 3 - 4 times higher than the average occupational exposure, do not show statistically significant increase in the incidence of cancer or heritable genetic disorders

30. Radiation Effects on Embryo & Fetus: The principal factors are the dose, dose rate and stage of gestation at which the dose is delivered Total developmental period of embryo & fetus in uterus is divided into 3 stages: Pre-implantation : Time b/w fertilization to attachment of embryo to uterus wall (0 to 8 days) Most sensitive stage Effect is termed as All-or-Nothing 0.1Gy is also may cause lethality

31. Radiation Effects on Embryo & Fetus: Organogenesis : Major organs developing stage (9 to 60 days) Exposure during early organogenesis exhibits greatest intrauterine growth retardation (more radio sensitive cells) A dose of order of 3.5 to 4Gy seems great enough to cause a miscarriage in most cases 300mSv is threshold exposure limit of mental retardation in this stage

32. Radiation Effects on Embryo & Fetus: Fetal Period : Growth of the structures (60 to 270 days) A variety of effects have been documented after exposure Higher doses of radiation required to lethality during this period than earlier stages Permanent growth retardation observed In Japanese survivors, irradiation of utero results small head size, mental retardation etc., Finally to be safer side, it must be assumed that the entire period of gestation from 10 days to 25weeks is sensitive to induction of malformations by radiation

33. Radiation Effects on Embryo & Fetus:

34. Application Occupational Exposure Dose limit Whole body Effective Dose 20 mSv/year (averaged over defined period of 5 years, with not more than 50 mSv in single year) In INDIA, this provision is limited to 30 mSv should not exceed in any single year Parts of Body: Equivalent Dose Lens of Eye 150 mSv/year Skin 500 mSv/year (Averaged over areas of no more than any 1 cm 2 regardless of the area exposed and nominal depth is 7.0mg/cm 2 ) Head & Feet 500 mSv/year (Averaged over areas of the skin not exceeding 100 cm 2 ) Occupational Exposures

35. Application Public Exposure Dose limit Whole body Effective Dose 1 mSv/year (averaged over defined period of 5 years, with not more than 5 mSv in single year) Parts of Body: Equivalent Dose Lens of Eye 15 mSv/year Skin 50 mSv/year (Averaged over areas of no more than any 1 cm 2 regardless of the area exposed and nominal depth is 7.0mg/cm 2 ) Head & Feet 50 mSv/year (Averaged over areas of the skin not exceeding 100 cm 2 ) Public Exposures

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