Biological Effects of Ionising Radiation

Radiobiology is a field of clinical medical sciences that involves the study of the action of ionising radiation on living things, especially health effects of radiation.

Becquerel (Bq) is a measure of radioactivity (atom decays over time) – so how many apples are falling out of the tree Bq=disintegrations/second Gray (Gy) is a measure of absorbed dose – how many apples are hitting the person Gy=1 joule of radiation per kg of matter Sievert (Sv) is a measure of effect on the body based on the size and shape of the apples, where the body was hit Sv=equivalent biological effect of 1 joule/kg

Linear Energy Transfer (LET)

Linear Energy Transfer (LET)

Linear Energy Transfer (LET) + LET is the rate at which energy is deposited as a charged particle or photon travels through matter + Heavier particles with a larger charge produce higher ionisation density + For a given particle type, as the velocity and energy goes up, the density of ionisation (and therefore LET) reduces

Alpha particles LET=100-200keV/ μm 14MeV neutrons LET=12keV/ μm 250kVp xrays LET=2keV/ μm 4MeV xrays LET=0.3keV/ μm

+ Absorbed dose can be a poor indicator of the biological effect of radiation + Biological effect can depend on many factors: type of radiation, initial energy and type of tissue 1Gy of neutrons produce a greater biologic effect than 1Gy of xrays due to the difference in the pattern of energy deposition + RBE is the ratio of biological effectiveness of one type of ionising radiation compared to another

+ Direct damage of radiation causes a disruption in the atomic structure which produces chemical and biological changes to the DNA + Indirect damage of radiation is caused by the free radicals, which come from the ionisation or excitation of the water component in the cells by producing a hydroxyl radical (this accounts for 2/3rds of radiation damage)

direct damage - double strand break/ single strand break cell death - apoptosis indirect damage free radicals and reactive oxygen species o2 - OH, h2O2 etc double strand break/ single strand break cell death

The cell cycle + G1 phase= Metabolic changes prepare the cell for division – signal is given to divide + S phase= DNA synthesis and replicates the genetic material each 46 cell is duplicated + G2 phase= Metabolic changes necessary for mitosis and cytokinesis cell checks the duplicated chromosomes for errors checks any errors. - check point gene - cell divides mitosis + M phase= A nuclear division (mitosis) followed by a cell division (cytokinesis). if you don’t have good checkpoint genes your cells will be sensitive to radiation - cells are killed easier - could be become cancerous

Cell check point genes + Cell cycle progression is monitored by molecular check point genes + Genes involved in radiation effects halts in G2 so that damage can be checked, and reparation started before mitosis is started + Cells which lack check point genes are sensitive to radiation-induced cell kill and carcinogenesis genomicnic instablity - cells find it hard to repair

Mechanism of cell death + Mitotic death: when cells die attempting to divide (most common) + Apoptosis: naturally programmed cell death + Bystander effect: cells directly affected by radiation release cytotoxic molecules prompting death in neighbouring cells

Types of cell death The definition of cell kill varies depending on the type of tissue: + Differentiated cells which do not proliferate (nerves, muscles, secretory) are defined as loss of a specific function. + Proliferating cells (stem cells in bowel) are defined as a loss of reproductive capacity.

Early and late responding tissues + Rapidly dividing cells respond early to radiation damage (skin, intestinal epithelium, bone marrow) + Late responding tissues (spinal cord, lung, kidney) + All tissues have a natural tolerance for radiation damage

Cancer Cancer occurs when a normal cell: + has a mutation/loss of cell check point genes + loses the ability to stop reproducing + loses the ability to undergo apoptosis

Stochastic effects Cancer Genetic effects Somatic mutations deterministic effects Cataract Erythema Infertility

Stochastic * Mechanism is cell modification * Probabilistic in nature * Probability increases with dose * Cannot be completely avoided * Relationship cannot be established * Occurs in a small percentage of population Deterministic * Mechanism is cell killing * Has a predictable threshold dose * Severity increases with dose * Can be completely avoided * Sure to occur at an adequate dose * Will occur in all population

Low Sensitivity - mature red blood cells muscle cells ganglion cells mature connective tissues high sensitivity - gastric mucosa mucous membranes oesophageal epithelium urinary bladder epithelium Very High Sensitivity Primitive blood cells Intestinal epithelium Spermatogonia Ovarian follicular cells Lymphocytes

Radiation protection + We want to eliminate ability of deterministic to occur Example: Skin erythema + We want to reduce the probability of the occurrence of stochastic effects Example: secondary cancers

justification limitation optimisation

limit time increase distance use shielding