radbio finals

• Mutagenesis


  The process by which the genetic information of an organism is changed, resulting in a mutation
• H.J. Muller reported the results of his irradiation of Drosophila, the fruit fly


  1927
• Genetic effects of radiation


  • They are linear, non-threshold
  • Radiation does not alter the quality of mutations but rather increases the frequency of those mutations
• Russel began to irradiate a large mouse colony with different radiation dose rates


  1946
• Russel's conclusions


  • A dose rate does exist
  • The mouse has capacity to repair genetic material
  • He confirmed the linear, non-threshold form of dose-response relationship
  • He has not detected any types of mutations that did not occur naturally
• Additional conclusions about radiation-induced mutations


  • They are usually harmful
  • Any dose of radiation, however small, to a germ cell results in some genetic risks
  • The effect depends on radiation protraction & fractionation
  • For most pre-reproductive life, the woman is less sensitive than the man to the genetic effects of radiation
  • Most radiation-induced mutations are recessive. Consequently, such mutations may not be expressed for many generations
  • The frequency of radiation-induced genetic mutations is extremely low. It is approximately 10-7 mutations / rad / gene
• Genetically significant dose (GSD)


  The average gonadal dose given to members of the population who are of childbearing age, that if received by every member of the population, would produce the total genetic effect on the population as the sum of the individual doses actually received
• Annual GSD in the US is 100 mRad/yr
• Low dose, chronic irradiation does not impair fertility
• Concerns about radiation exposure during pregnancy


  • Before pregnancy: interrupted fertility
  • During pregnancy: possible congenital effects in newborn
  • Post-pregnancy: suspected genetic effects
• Effects of irradiation in utero

  • Prenatal death
  • Neonatal death
  • Congenital malformation
  • Malignancy induction
  • General impairment of growth
  • Genetic effects
  • Mental retardation
• The first trimester during pregnancy is the most radiosensitive period
• The first 2 weeks of pregnancy may be of least concern because the response is all-or-nothing
• The relative risk of childhood leukemia after irradiation in utero is 1.5
• Spontaneous abortion after 10 rad in utero

  Least concern, rationale: all-or-none effect, time of exposure: 0-2 weeks, natural occurrence: 25%, radiation response: 0.1%
• Congenital abnormalities after 10 rad in utero

  Time of exposure: 10 weeks, natural occurrence: 5%, radiation response: 1%
• Malignant disease after 10 rad in utero


  Time of occurrence: 0-9 months, natural occurrence: 8/10,000, radiation response: 12/10,000
• Impaired growth and development after 10 rad in utero


  Time of occurrence: 0-9 months, natural occurrence: 1%, radiation response: nil (non-existent)
• Genetic mutation after 10 rad in utero


  Time of occurrence: 0-9 months, natural occurrence: 10%, radiation response: nil (non-existent)
• Linear energy transfer (LET)


  A measure of the rate at which energy is transferred from ionizing radiation to soft tissue. As LET increases, the biological effectiveness increases.
• Relative biological effectiveness (RBE)


  Ratio of the dose of standard radiation necessary to produce a given effect to the dose of test radiation needed for the same effect
• Protraction


  The dose is delivered continuously but at a lower dose rate
• Fractionation


  The dose is delivered at the same dose in equal portions at regular intervals
• Protraction and fractionation reduce the radiation effect
• Oxygen effect


  Oxygenated/Aerobic tissue is more sensitive to radiation than anoxic & hypoxic tissue
• Radiosensitivity by age


  • Before birth: most radiosensitive
  • After birth: radiosensitivity decreases
  • Maturity: most radioresistant
  • Old age: somewhat more radiosensitive
• Recovery


  • Intracellular repair + Repopulation
  • Intracellular repair is due to a repair mechanism inherent in the biochemistry of the cell
  • Repopulation is replication by surviving cells
• Radiosensitizers


  • Halogenated pyrimidines
  • Hydroxyurea
  • Methotrexate
  • Vitamin K
  • Actinomycin D
• Radioprotectors


  • Cysteine
  • Cysteamine
• Hormesis


  A little bit of radiation is good for us, as it stimulates hormonal & immune responses to other toxic environmental agents
• Stochastic effects


  Late effects of radiation
• Principal late effects


  • Radiation-induced malignancy
  • Genetic effects
• Other late effects


  • Shortening of life span
  • Local tissue effect
• Radiation exposure experienced by personnel


  • Low dose and low LET
  • Chronic in nature
  • Delivered intermittently over long periods

  
• Dermatitis


  • Developed on early radiologists who performed fluoroscopic examination
  • Skin appearance: callused, discolored and weathered (hands and forearms)
  • Skin characteristics: very tight, brittle and severely crack or flake
• Early response to irradiation of blood-forming organs

  • Hematologic depression
• Late response to irradiation of blood-forming organs


  • Leukemia
  • Irradiation of circulating lymphocytes
• Early and late response to irradiation of blood-forming organs

  • Chromosome damage
• Radiation-induced cataract


  • It occurs on the posterior pole of the lens
  • Dose-response relationship: nonlinear, threshold
  • Radiosensitivity of the lens: age-dependent

  
• Increased age


  • Greater radiation effect
  • Shorter latent period
  • 5-30 years
  • Average: 15 years