Late Deterministic and Stochastic Radiation Effects on Organ Systems PDF

Late Deterministic and Stochastic Radiation Effects on Organ Systems ■ By ■ Dr. Mohsen Dashti ■ 432 Radiation Protection & Radiobiology SOMATIC EFFECTS ■ When living organisms that have been exposed to radiation sustain biologic damage, the effects of this exposure are classified as somatic (i.e.,...

Late Deterministic and Stochastic Radiation Effects on Organ Systems ■ By ■ Dr. Mohsen Dashti ■ 432 Radiation Protection & Radiobiology SOMATIC EFFECTS ■ When living organisms that have been exposed to radiation sustain biologic damage, the effects of this exposure are classified as somatic (i.e., body) effects – An example of a non- somatic effect is irradiation of an individual’s genetic material (sperm or eggs) leading to a genetic malformation in offspring. This lecture focuses on organic damage from ionizing radiation that occurs months or years following radiation exposure. STOCHASTIC  The probability of the effect, rather than its severity, ↑ with dose  No dose respond threshold below which risks cease to exist (modern radiation program) ALARA, as low as reasonably achieved.  The principal health risk from low-dose radiation  Radiation-induced cancer and genetic effects LATE SOMATIC EFFECTS: are consequences of radiation exposure that appear months or years after such exposure.  These effects may result from the following:  Previous whole- or partial-body acute exposure  Previous high radiation doses  Long-term low-level doses sustained over several years.  The three major types of late effects are:  Carcinogenesis (STOCHASTIC)  Embryologic effects (STOCHASTIC)  Cataractogenesis (DETERMINSTIC)      DETERMINISTIC Threshold dose below which the effect is not seen. Associated with relatively high doses(>2 Gy) Severity of the effect, rather than its probability, ↑ with dose. Predominant biologic effect is cell killing resulting in degenerative changes to the exposed tissue Cataracts, erythema, fibrosis, and hematopoietic damage are some deterministic effects  Risk Estimate for Cancer from Low-Level Radiation Exposure(stochastic effect)  LOW-LEVEL RADIATION has been defined as “an absorbed dose of 0.1 Sv or less delivered over a short period of time” and as “a larger dose delivered over a long period of time—for instance, 0.5 Sv in 10 years.”  Does the dose in radiography considered as low-level exposure??  The effective dose of a typical routine two-view chest radiograph is approximately 0.06 (can be greater or lesser, depending on the patient’s body habitus), so this is considered far lower than what is considered a low-level exposure.  Low-level radiation defined in broad terms to include the various sources of ionizing radiation, such as:  X-rays and radioactive materials used for diagnostic purposes in the healing arts  Employment-related exposures in medicine and industry  Natural background exposure  The risk estimate for humans getting cancer from low-level radiation exposure is still controversial.  No conclusive proof exists that low-level ionizing radiation doses below 0.1 Sv cause a significant increase in the risk of malignancy.  The risk, in fact, may be negligible or even nonexistent.  Using all data available on high radiation exposure, members of the scientific and medical communities determined that three categories of adverse health consequences require study at low levels of exposures:  Cancer induction  Damage to the unborn from irradiation in utero  Genetic (hereditary) effects Risk Estimates for Cancer.  At low doses, below 0.1 Sv, which includes groups such as occupationally exposed individuals and virtually all patients in diagnostic radiology, this risk is not directly measurable in population studies. Either the risk is overshadowed by other causes (e.g., environmental exposures, genetic predisposition, lifestyle factors such as smoking) of cancer in humans or the risk is zero.  Current radiation protection philosophy assumes that risk still exists and may be determined by EXTRAPOLATING (SCALING DOWN THE RISK-VERSUS-DOSE CURVE) FROM HIGH-DOSE DATA, in which risk has been directly observed, down to low doses, in which it has not been observed. This remains a very controversial concept. MODELS FOR EXTRAPOLATION OF CANCER RISK FROM HIGH-DOSE TO LOW-DOSE DATA. ■ Researchers commonly use two models for extrapolation of risk from high-dose to lowdose data – linear – linear-quadratic models.  RADIATION DOSE-RESPONSE RELATIONSHIP ■ Radiobiologists engaged in research have a common goal to establish relationships between radiation and dose response. The information obtained can be used to attempt to predict the risk of occurrence of malignancies in human populations that have been exposed to low levels of ionizing radiation. ■ Radiation dose-response relationship is demonstrated graphically through a curve that maps the observed effects of radiation exposure in relation to the dose of radiation received. ■ The curve is either linear (straight line) or nonlinear (curved to some degree), and it depicts either a threshold dose or a nonthreshold dose ( Fig. 9-1 ).  Risk Model Used to Predict High Dose Cellular Response  THRESHOLD (DETERMENSTIC) below a certain radiation level or dose, no biologic effects are observed. Biologic effects begin to occur only when the threshold level or dose is reached.  LINEAR THRESHOLD DOSE-RESPONSE CURVE  SIGMOID, OR S-SHAPED ( NONLINEAR ), THRESHOLD CURVE  Risk Models Used to Predict Cancer Risk and Genetic (Hereditary) Damage in Human Populations (low level radiation)  NONTHRESHOLD: indicates that any radiation dose has the capability of producing a biologic effect. – NO RADIATION DOSE CAN BE CONSIDERED ABSOLUTELY “SAFE.” – Currently, advocates of this point of view theorize that because all radiation exposure levels possess the potential to cause biologic damage, then radiographers must never fail to employ aggressive radiation safety measures whenever humans are exposed to radiation during diagnostic imaging procedures.  LINEAR NONTHRESHOLD CURVE MODEL (LNT)  LINEAR-QUADRATIC NONTHRESHOLD CURVE ( LQNT )  LINEAR THRESHOLD DOSE-RESPONSE CURVE  Describe the Deterministic effects of significant radiation exposure such as skin erythema and hematologic depression  Biologic response does not occur below a specific dose level.  Laboratory experiments on animals and data from human populations observed after acute high doses of radiation provided the foundation for this curve.  SIGMOID, OR S-SHAPED ( NONLINEAR ), THRESHOLD CURVE  Employed in radiation therapy to demonstrate high-dose cellular response to the radiation within specific tissues such as skin, lens of the eye, and various types of blood cells.  Different effects require different minimal doses.  The tail of the curve indicates that limited recovery occurs at lower radiation doses.  At the highest radiation doses, the curve gradually levels off and then veers downward because the affected living specimen or tissue dies before the observable effect appears. LINEAR NONTHRESHOLD CURVE MODEL (LNT)  Linear curve implies that biologic response to ionizing radiation is directly proportional to the dose received.  Currently, Committee on the Biological Effects of Ionizing Radiation BEIR recommends use of LNT dose-response model for most types of cancers.  Epidemiologic data about the Hiroshima atomic bomb survivors also indicate that a linear relationship exists between radiation dose and radiation-induced leukemia.  But it exaggerate the seriousness of radiation effects at lower dose levels from low-LET radiation. However, it accurately reflects the effects of high-LET radiation (neutrons and alpha particles) at higher doses.  In establishing radiation protection standards, the regulatory agencies have chosen to be conservative—that is, to use a model that may overestimate risk but is not expected to underestimate risk. LINEAR-QUADRATIC NONTHRESHOLD CURVE ( LQNT )  LINEAR-QUADRATIC curve states that the equation that best fits the data has components that depend on dose to the first power (linear or straightline behavior) and also dose squared (quadratic or curved behavior).  (BEIR) committee revealed that, most stochastic effects (e.g., cancer) and genetic (hereditary) effects at low dose levels from low–linear energy transfer (LET) radiation, such as the type of radiation used in diagnostic radiology, appear to follow a LQNT curve model.  The following health concerns are presumed to follow this curve: – Leukemia – Breast cancer – Heritable damage Carcinogenesis. ■ Cancer is the most important late stochastic effect caused by exposure to ionizing radiation. ■ Cancer is a random occurrence that does not seem to have a threshold and for which the severity of the disease is not dose related (e.g., a patient’s leukemia induced by a low-dose exposure is no different from a person’s leukemia that was caused by a high-dose exposure).  Cancer caused by low-level radiation is difficult to identify.  Human evidence of radiationinduced carcinogenesis comes from the observation of irradiated humans and from epidemiologic studies conducted many years after subjects were exposed to high doses of ionizing radiation.  Examples of these data are listed in Box 9-2 . ■ Cataractogenesis. ■ The lens of the eye contains transparent fibers that transmit light. The lens focuses light on the retina so that as the image forms, it may be transmitted through the optic nerve. ■ The probability that a single dose of ionizing radiation of approximately 2 Gy will induce the formation of cataracts (opacity of the eye lens) is high. ■ Cataracts result in partial or complete loss of vision. ■ Laboratory experiments with mice show that cataracts may be induced with doses as low as 0.1 Gy. Highly ionizing neutron radiation is extremely efficient in inducing cataracts. ■ A neutron dose as low as 0.01 Gy has been known to cause cataracts in mice. ■ Radiation induced cataracts in humans follow a threshold. Embryologic Effects (Utero)  Developing embryo is characterized by the rapid cells proliferation, migration, and differentiation. Thus is extremely sensitive to ionizing radiation.  Response depends on a number of factors including (1) total dose, (2) dose rate, (3) radiation quality, and (4) the stage of development at the time of exposure.  Effects if any as Prenatal or neonatal death Congenital abnormalities Growth impairment Reduced intelligence Genetic aberrations Increase in future risk of cancer. The period of gestation during which the embryo-fetus is exposed to radiation governs the effects (death or congenital abnormality) of the radiation. Three stages of fetal development: 1. Pre-implantation:  begins with the union of the sperm and egg (conception) and continues through day 9 in humans.  if irradiated with a dose in the range of 0.05 to 0.15 Gy, embryonic death will occur.  For doses less than 100 mGy, the risks are very low.  all-or-nothing response. 2. Major organogenesis:  period from second to eighth week after conception.  Congenital Abnormalities occurring as a consequence of irradiation during the period of organogenesis may include: Growth inhibition, Mental retardation, Microcephaly, Genital deformities and Sense organ damage  only CNS shown an association between malformations and low-LET radiationin doses less than 250 mGy. – The central nervous system in the growing human fetus remains undifferentiated and does not normally complete development until approximately the twelfth year of life. 3. fetal stage:  from end of 6th week post conception  Fewer abnormalities, decreased incidence of prenatal and postnatal death. Relative sensitivity for radiation-induced effects during different stages of fetal development.