Toxicology of radioactive substances

    Radiation can be ionizing radiation or non ionizing radiation.

• Ionizing Radiation is defined as radiation capable for producing ions when interacting with matter –in other words enough energy to remove an electron from an atom. In general, ionizing radiation reduces the rate of metabolism of xenobiotics both in vivo and in enzyme preparations subsequently isolated.
• Nonionizing radiation has less energy and, in general, is less interactive with biological material than ionizing radiation.
• Sources of non-ionizing radiation include – Ultraviolet light, visible light, infrared radiation, microwaves, radio & television, power transmission

 Sources:       

    X-rays

• Radioactive material produce alpha, beta, and gamma radiation
• Cosmic rays from the sun and space.
• The four main types of irradiation are X-rays, gamma rays, electrons (negatively charged beta particles or positively charged positrons) and alpha particles.
• Alpha particles: Emitted from nucleus of radioactive atoms
• Beta –particles: Emitted from nucleus of radioactive atoms
• Gamma-particles: Emitted from nucleus of radioactive atoms –spontaneous Emitted with kinetic energy related to radioactive source.
• X-rays

IRRADIATION-SENSITIVITY, HALF LIFE, EXPOSURE, ABSORPTION

Tissue Sensitivity to irradiation

• Very high – White blood cells (bone marrow), intestinal epithelium, reproductive cells • High – Optic lens epithelium, esophageal epithelium, mucous membranes
• Medium – Glial cells of brain, lung, kidney, liver, thyroid, pancreatic epithelium
• Low – Mature red blood cells, muscle cells, mature bone and cartilage.

 Half – life

• Rate of decay of radioisotope
• This can range from very short to billions of years .
• Half life of carbon is about 5730 years .

Reducing exposure to radiation can be achieved by

• Time – Reduce the spent near the source of radiation.
• Distance – Increase the distance from the source of radiation.
• Shielding – Place shielding material between you and the source of radiation.

 Absorption of Radiation

• Absorption of radiation is the prime consideration in radiation toxicology.
• Radiation can reach all tissues of the body directly from an external source, but the capacity to penetrate body tissues varies with the type of radiation.
• Radiation may be emitted as particles or as high-energy electromagnetic waves such as X-rays or gamma radiation.
• -particles released by radionuclides are dangerous if they are taken into the body by α inhalation (breathing in) and/or ingestion (eating and drinking).
• The adverse health effects caused by radon, an -emitter, are explained by -particles α α that are absorbed in the lung, thus becoming an internal radiation source.
• Indoor radon exposure can lead to lung cancer.
• Exposure from radon in drinking water is also of toxicological importance
• The depth to which ß-particles can penetrate the body depends upon their energy.
• When ß -emitters are taken into the body they irradiate internal tissues and become a more serious hazard.

Mechanism of action

Can be explained by two ways:

1. Direct effects
2. Indirect effects

            1.Direct effects:

Direct transfer of radiation energy to molecules of cells (esp. DNA) causing ionization and breakage of linkage. Eg. Beta rays, alpha rays, gama rays, neutrons

2. Indirect effects:

Formation of free radicals which react with macromolecule (nucleic acids, amino acids, proteins. Lipids, CHO) and cause variety of genetic and non genetic damage. Eg. H20 > H2+ & OH- (highly reactive) which react and produce H2O2 (react with macromolecule).

Clinical Signs:

1. Acute radiation toxicity:-

• Acute irritation of alimentary tract resulting intense and refractory diarrhoea.
• Redness of skin.
• Excessive thirst, Weakness.
• Recumbency, Laboured breathing.
• Profuse nasal discharge containing blood.
• Impaired blood clotting and antibody production.
• Gradual loss of hair.
• Ulceration of skin.
• Cataract, Genetic mutation.
• Death within 1-4 week

2. Sub-acute radiation toxicity:-

•  
•  
• Depression
• Swelling of legs.
•  
• Dysentry , Anemia.
• Laboured breathing
• Alopecia, Sterility.
• Ulceration of skin.
• Hyper irritability
• Embryonic death.
• Newborn mortality
• Stunted grown

3. Chronic radiation toxicity:-

• Alopacia
• Sterility
• Genetic mutation.
• Leukemia
• Tumors of thyroid, lungs and breast.
• Stunted growth.
• Embryonic death.

PM lesions:

• Hemorrhagic & Ulcerative gastro-enteritis.
• Ulceration of physiological mucosa.
• Pulmonary edema.
• Extra-vasation of fluid.
• Fibrinous pneumonia.
•  
• Changes of color of bone marrow.

Diagnosis:

• History, clinical signs and PM lesions
• Lymphocyte count- decrease

            Treatment:

• No specific treatment
• Supportive therapy
• Antibiotics- secondary infection
• Fluid electrolyte therapy
• Corticosterois and anti-histaminic cream-for skin ulcer and inflammation

Corticosteroids decreases severity of desquamation reaction.

• Fresh bone marrow cell transfusion.
• Parathyroid extracts and low calcium diets ( increase excretion of radioactive materials).