Genetic Effects to the Fetus Chapter 5

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Genetic Effects to the Fetus Chapter 5

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Genetic Damage, Irradiation to the fetus, and Stochastic/ nonstochastic Effects :Genetic Damage, Irradiation to the fetus, and Stochastic/ nonstochastic Effects Presented By: Nabil Ortega


Objectives :Objectives Discuss GSD Discuss irradiation of the fetus Describe and discuss the three stages of the fetus Describe the principle effects of irradiation to the fetus Explain the stochastic and nonstochastic effects


Genetic Damage :Genetic Damage Muller’s study concluded that: No new or unique mutations are produced by radiation In the dose range of 25-400 R, the frequency of mutations was linear with dose The majority of radiation induced mutations were recessive. Both parents would have to carry the gene for an effect to be observed in the off spring. There were no dose rate or dose fractionation effects.


Genetic damage cont. :Genetic damage cont. Epidemiologic studies have not demonstrated radiation-induced genetic effects Largest population studied is that of the atomic bomb survivors and their offspring Blood screening of 27,000 children of atomic bomb survivors for 28 specific that may have been caused by radiation exposure protein loci demonstrated only 2 mutations Genetically Significant Dose (GSD) An average calculated from the gonadal dose received by the entire population The annual GSD from all radiation sources is approximately 130 mrem Single largest contribution is natural background with 102 mrem


Irradiation of the fetus :Irradiation of the fetus Based on the Law of Bergonie and Tribondeau (developing embryo is very radiosensitive) Embryo's response to irradiation depends on: Total dose Rate of dose Quality of radiation Stage of development The principle effects of irradiation to the fetus include: Prenatal or neonatal death Congenital abnormalities Growth impairment Reduced intelligence Genetic abnormalities Cancer induction


Irradiation of the fetus Cont. :Irradiation of the fetus Cont. Data on the effects of irradiation in utero were obtained by offspring from the atomic bomb survivors Microcephaly and mental and growth retardation were main abnormalities seen Abnormalities in eyes, genitals and skeleton occurred less often Children from Hiroshima and Nagasaki who were irradiates in utero between 8 to 25 weeks postconception demonstrated lower IQ Also children were observed to have microcephaly


Irradiation of the fetus Cont. :Irradiation of the fetus Cont. A fetus undergoes 3 stages of development: Pre-implantation Major organogenesis Fetal/growth stage


Pre-Implantation Stage :Pre-Implantation Stage Originates with the joining of the sperm and the egg Radiation damage during this stage can cause prenatal death Factors that can contribute to the cell’s resistance to radiation induced abnormalities include their capability of repair, undifferentiation, and hypoxic state of the embryo Loss of sex chromosome in female can cause Turner’s Syndrome Endocrine disorder caused by failure of the ovaries to respond to pituitary hormone simulation classical features of Turner's syndrome: (A) short webbed neck; (B) cubitus valgus; (C) lymphedema.


Major Organogenesis :Major Organogenesis Takes place within the 2nd to 8th week after conception The CNS is the only organ system that has shown a relationship between congenital abnormalities and low LET Because of the depletion of cells, embryos that are irradiated early in organogenesis show the greatest retardation of growth Atomic bomb survivors who received in utero exposure more than 10 rads showed increase in microcephaly


Fetal Growth Stage :Fetal Growth Stage Starts following the end of major organogenesis at day 45 Effects the nervous systems and sense organs Damage during this stage may manifest later; for example behavioral changes, reduced IQ, or cancer Leukemia mortality are 2-3/10,000 after 1 rad of low LET radiation Solid tumors occur at same incidence Current effective dose equivalent limit to fetus is no more than 500mrem during the gestational period


Stochastic and Nonstochastic Effects :Stochastic and Nonstochastic Effects Stochastic effects occur randomly in nature Thought to be nonthreshold as damage to a few cells or even a single cell can produce the disease Regarded as the main health risk from low dose radiation from exposure in the radiology field Radiation induced cancer and radiation induced genetic effects Nonstochastic effects Also known as deterministic effects Catarast, erythema, fibrosis and hematopoietic damage Needed a much higher dose


Work Cited :Work Cited http://wonder.cdc.gov/wonder/prevguid/p0000419/p0000419.asp#head002004002000000 www.google.com/geneticeffects http://microbiology.mtsinai.on.ca/faq/transmission.shtml


Summary :Summary GSD is an average calculated from the gonadal dose received by the entire population A fetus undergoes 3 stages of development: Pre-implantation, Major organogenesis, Fetal/growth stage The principle effects of irradiation to the fetus include: Prenatal or neonatal death, Congenital abnormalities,, Growth impairment, Reduced intelligence Because of the depletion of cells, embryos that are irradiated early in organogenesis show the greatest retardation of growth


Questions :Questions 1. What is GSD and what does in stand for? Is an average calculated from the gonadal dose received by the entire population; Genetically Significant Dose 2. An embryo's response to irradiation depends on __________, ___________, ___________, and __________. Total dose, rate of does, quality of radiation, and stage of development 3. Name at least 2 principle effects of irradiation to the fetus. Prenatal or neonatal death, Congenital abnormalities, Growth impairment, Reduced intelligence, Genetic abnormalities, Cancer induction 4. A fetus undergoes three stages of development. These include pre-implantation, ______________, and fetal/growth stage. Major organogenesis


Questions :Questions 4. Following implantation, doses of at least ______ are necessary to cause prenatal death. 25 rads 5. During what period of conception does major organogenesis take place? 2nd to 8th week after conception 6. Atomic bomb survivors who received in utero exposure of more than 10 rads showed increase in ________________. Microcephaly 7. In the fetal stage, damage during this stage may manifest later. Give the 3 examples of what that were stated earlier. behavioral changes, reduced IQ, or cancer


Questions :Questions 8. Current effective dose equivalent limit to fetus is no more than ____________. 500 mrem 9. Give an example of stochastic and nonstochastic effects. Radiation induced cancer; catarats 10. Explain the difference between stochastic and nonstochastic.


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