Radiosensitivity

Definition

• The relative susceptibility of the cell to the radiation effect is referred as radiosensitivity

Factors affecting Cellular Radiosensitivity

• Conditional Radiosensitivity• Inherent Radiosensitivity

Conditional Factors

• Dose Rate• LET• Presence of Oxygen

Effect of Dose Rate

Effect of Radiation Dose Fractionation

Effect of LET

Effect of Oxygen

Inherent Factors

• 1. Law of Bergonie and Tribondeau states that radiosensitivity is greatest for those cells that a. Have a high mitotic rate

b. Have a long mitotic future c. are undifferentiated

Phases of cell’s Reproductive cycle

• 2. Law of Ancel & Vitemberger • It states the inherent susceptibility of any cell

to damage by radiation is the same, but the time of appearance of radiation-induced damaged differs among different types of cells

• The appearance of radiation damage depend a. Biologic Stress to the cell b. the condition to which the cell is exposed

pre and post irradiation.

• 3. Sparrow Hypothesis the radio sensitivity is directly proportional to

the interface chromosomal volume.

LD (50/30) Effect

• The radiation dose required to kill 50% of the cell population within 30 days of irradiation

LD(50/30) effect on skin

LD (50/30) on Eye and Blood forming organs

• Refer class notes

LD (50/30) effect on Embryo

• Exposure of 1-2 Gy of X ray or Gamma ray can produce pre natal or neo natal death, growth disturbances, organ malformation and impairment of adult physiology

• The effects of radiation on the fetus depend on two factors: dose and stage of development at the time of exposure.

• Between conception & birth the fetus passes thru 3 basic stages of dev’t

1. Pre-implantation (day 1 to 10)

2. Organogenesis (day 11 to 42)

3. Growth Stage (day 43 to birth)

• Pre-implantation period: Excess of 250 mGy radiation

exposure induces prenatal death.

• Organogenesis period: Radiation exposure induces

neo-natal death and will result in retardation in growth ( poor dev’p of brain, eye, skeleton), mainly embryonic malformation

• Fetal or Growth period: Radiation exposure can induce

organ growth retardation, reduced IQ or behavioural alteration in life (later)

• Radiation dose below 1 Gy produces reduction in brain size (microcephalous) & hence mental retardation

• The period of 3 to 15 week of gestation is more radiation sensitive ( eq: radiation effect include small head in children)

• the diagnostic exposure of women during pregancy might result in Leukemia(blood cancer) and other cancer in their children at younger age (15 years)

LD 50/30 on Endocrinal Glands

• Reproductive System- Gonads ( testis in male

and Ovaries in female)- Cells of it are highly

radiosensitive- Dose(6 Gy) permanently

sterilizing males. (sterility occur after a few month)

- Lower doses can cause sterility afer several months of irradiation (temporary effect)

- Radiation destroys both ovum & maturing follicles- results in reduction of hormone production

• Radiation dose & age – important factors in radiation effects

• Thyroid Gland- result in hypothyroidism

(‘decrease in production of thyroxine’) which cause a lower metabolic rate.

- Symptoms: feeling tired, restless, problem in concentrating, feeling sad/ depressed,Mood changes, Constipation, Feeling cold all the time, puffiness around the eyes.

• Pancreas- Radiation effect: Diabetic

mellitus

• Hypothalamus & Pituitary Gland

- Hypothalamus appear to be more radio sensitive than the pituitary gland and may be damaged by lower radiation doses (< 40 Gy)

- Higher doses: damage both hypothalamus & pituitary gland.

- Radiation Effects: Hypopituitarism, Central Hypothyroidism, Central Adrenal Insufficiency

• Adrenal Gland- Radiation effect: Addison’s

disease (Adrenal insufficiency)

- Deficiency of cortisol.- It is characterised by muscle

weakness, reduced blood sugar, nausea, loss of appetite, weight loss, low B.P.

• Pineal Gland- Results in change in

melatonin level which causes several disorder like cancer, sexual dysfunction & hypertension

• Thymus Gland- Radiation effect in

thymus Results in disease which are caused by a damaged and a weak immune system

Linear No-Threshold Risk Model

• Linear- An increase in dose results in a proportional increase in risk

• No- Threshold: Any dose, no matter how small, produces some risk

Factors affecting Frequency of Radiation induced Mutation

• Radiation Dose and Fractionation- The mutation frequency is linearly dependent

on the dose- The mutation frequency (MF) is lower, if the

dose is given in fractions ( due to enzymatic DNA repair mechanism)

• Time interval b/w irradiation & conception- MF decreases as time interval increases

Cond

• Age & Sex- The MF is higher for young patients i.e. the MF

decreases as the age increases- MF is lower for female compared to males

Gene Controlled Hereditary Diseases

• The abnormality that is carried on for the future generation – Hereditary Disease

• If the abnormality is due to the DNA alteration (change in gene sequence) : Gene controlled Hereditary Disease.

• Basic types of Genetic Disorder: 1. Single Gene or Mendelian Disorder 2. Multifactorial or Complex Disorder

Cont 3.Mitochondrial Disorder 4. Chromosomal Disorder 5. Epigenetic Disorder : the disorder is in the gene

activity rather than the DNA structure Inheritance Pattern 1.Recessive : Both copies of the genes are

defective. Eg- Sickle cell Anaemia 2. Dominant : Only one copy of the gene is

defective. Eg- Marfan syndrome 3. X-linked disease: the recessive X type

chromosome are affected Eg- Haemophilia