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  /Author (Molly)
  /Subject (3.9 Hereditary Effects and Irradiation In Utero Cheat Sheet)
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    \vspace{-2pt}\large{\bf{\textcolor{DarkBackground}{\textrm{3.9 Hereditary Effects and Irradiation In Utero Cheat Sheet}}}} \\
    \normalsize{by \textcolor{DarkBackground}{Molly} via \textcolor{DarkBackground}{\uline{cheatography.com/30516/cs/9609/}}}
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  \mymulticolumn{1}{p{5.377cm}}{\bf\textcolor{white}{Cheat Sheet}}  \\
   \vspace{-2pt}Not Yet Published.\\
   Updated 25th October, 2016.\\
   Page {\thepage} of \pageref{LastPage}.
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\mymulticolumn{2}{x{5.377cm}}{\bf\textcolor{white}{Effect of Radiation on the Gonads}}  \tn
% Row 0
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{In general, the gonads are very radiosensitive but the biological effect of radiation varies considerably with the stage of development of the respective cells.} \tn 
% Row Count 4 (+ 4)
% Row 1
\SetRowColor{white}
\mymulticolumn{2}{x{5.377cm}}{{\bf{Testes}}} \tn 
% Row Count 5 (+ 1)
% Row 2
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{In the male, sperm production is continuous from puberty to death. The division of a spermatogonium (stem cell) to the development of a mature sperm takes about 10 weeks in man, and involves several different cell populations that vary in their sensitivity to radiation.} \tn 
% Row Count 11 (+ 6)
% Row 3
\SetRowColor{white}
\mymulticolumn{2}{x{5.377cm}}{Since the spermatogonia are relatively radiosensitive and the mature spermatozoa are relatively radioresistant, the effect of radiation on fertility is not apparent immediately. After exposure to a moderate dose of radiation, the individual remains fertile as long as mature sperm cells are available, but decreased fertility or even temporary sterility follows when these are used up.} \tn 
% Row Count 19 (+ 8)
% Row 4
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{Most of the results regarding testicular irradiation have been obtained from radiation therapy experience. In humans, a dose above about 0.15 Gy may cause temporary sterility. A single dose of about 6.0 Gy or a fractionated dose of 15 Gy over 10 days will often induce permanent sterility. However, the induction of sterility in human males does not produce significant changes in hormone balance, libido, or physical capability.} \tn 
% Row Count 28 (+ 9)
% Row 5
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\mymulticolumn{2}{x{5.377cm}}{{\bf{Ovaries}}} \tn 
% Row Count 29 (+ 1)
% Row 6
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{The effects of radiation on the ovaries are quite different from those on the testes.} \tn 
% Row Count 31 (+ 2)
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\vfill
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\begin{tabularx}{5.377cm}{p{0.4977 cm} p{0.4977 cm} }
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\mymulticolumn{2}{x{5.377cm}}{\bf\textcolor{white}{Effect of Radiation on the Gonads (cont)}}  \tn
% Row 7
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{All oocyte production (about seven million) occurs in the embryo where the ovum, surrounded by a single cell layer, is known as a primordial follicle and after the foetal stage they no longer divide.} \tn 
% Row Count 4 (+ 4)
% Row 8
\SetRowColor{white}
\mymulticolumn{2}{x{5.377cm}}{However, most of them soon degenerate so that less than two million are present in the two ovaries at birth, and only 300,000 at puberty. Then, during all the reproductive years of the female, only about 450 of these follicles develop enough to expel their ova; the remainder degenerate.} \tn 
% Row Count 10 (+ 6)
% Row 9
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{Therefore, in the adult there are no stem cells but there are three types of follicles: immature, nearly mature, and mature.} \tn 
% Row Count 13 (+ 3)
% Row 10
\SetRowColor{white}
\mymulticolumn{2}{x{5.377cm}}{Once again, from radiation therapy experience, it has been found that a dose of about 0.5 Gy may cause temporary sterility in some individuals, but a single dose of about 4 Gy or a fractionated dose of 15 Gy over 10 days will cause permanent sterility.} \tn 
% Row Count 19 (+ 6)
% Row 11
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{In contrast to the effect in males, though, pronounced hormonal changes comparable to those associated with the natural menopause accompany radiation-induced sterilisation in females.} \tn 
% Row Count 23 (+ 4)
\hhline{>{\arrayrulecolor{DarkBackground}}--}
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\mymulticolumn{2}{x{5.377cm}}{\bf\textcolor{white}{Radiation-Produced Mutations}}  \tn
% Row 0
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{It is a common misconception of the lay population that exposure to radiation can produce bizarre and even horrific mutants in future generations. In reality, however, radiation does not result in genetic effects that are new or unique but rather increases the frequencies of the same mutations that already occur spontaneously or naturally.} \tn 
% Row Count 7 (+ 7)
% Row 1
\SetRowColor{white}
\mymulticolumn{2}{x{5.377cm}}{Since radiation-produced mutations are identical in nature to those that occur spontaneously, you can appreciate that their study is particularly difficult and experimental sample sizes must be large in order to confidently detect those attributed to radiation as distinct from those that would otherwise appear.} \tn 
% Row Count 14 (+ 7)
% Row 2
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{{\bf{Animal Studies}}} \tn 
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% Row 3
\SetRowColor{white}
\mymulticolumn{2}{x{5.377cm}}{Estimation of hereditary risk is based almost entirely on the results of animal investigations. In an enormous biological experiment involving up to seven million mice (known as the 'Megamouse project'), the development of hereditary effects from radiation were observed and evaluated.} \tn 
% Row Count 21 (+ 6)
% Row 4
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{Radiation-induced genetic changes, like mutations from any other agent, may be a consequence of a gene mutation or chromosomal changes. {\bf{Mutation incidence has no threshold and is a linear function of dose}}; if the dose is doubled, the number of mutations is doubled.} \tn 
% Row Count 27 (+ 6)
% Row 5
\SetRowColor{white}
\mymulticolumn{2}{x{5.377cm}}{This has led to the concept of the {\bf{doubling dose}}, which is the dose of radiation required to double the spontaneous mutation rate, that is, the dose of radiation that would produce a number of mutations equal to the spontaneous or background level. Results from the mouse data support an approximate doubling dose of 1 Gy.} \tn 
% Row Count 34 (+ 7)
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\mymulticolumn{2}{x{5.377cm}}{\bf\textcolor{white}{Radiation-Produced Mutations (cont)}}  \tn
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\mymulticolumn{2}{x{5.377cm}}{{\bf{Human Studies}}} \tn 
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% Row 7
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\mymulticolumn{2}{x{5.377cm}}{Although many epidemiological investigations have been undertaken in humans, they have failed to demonstrate radiation-induced genetic effects. However, mutations of human cells have been identified in culture.} \tn 
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% Row 8
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{The largest population studied carefully for genetic effects is the survivors of the A-bomb attacks on Hiroshima and Nagasaki. Several genetic indicators have been studied for many decades in children born to the survivors. These include:} \tn 
% Row Count 11 (+ 5)
% Row 9
\SetRowColor{white}
\mymulticolumn{2}{x{5.377cm}}{1. stillbirths, major congenital defects, early death;\{\{nl\}\}2. childhood mortality; and\{\{nl\}\}3. sex chromosome abnormalities.} \tn 
% Row Count 14 (+ 3)
% Row 10
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{Parents of children studied came from both cities and from low (0.01 to 0.09 Gy) and high (more than 1 Gy) dose groups. Individuals from outside the cities were studied as controls. Though no genetic indicator has been found to be statistically significant, the average doubling dose has been estimated to be 1.56 Sv.} \tn 
% Row Count 21 (+ 7)
% Row 11
\SetRowColor{white}
\mymulticolumn{2}{x{5.377cm}}{In spite of this, numerical values of hereditary risk are currently based on a doubling dose of 1 Gy (equivalent dose of 1 Sv) and the ICRP estimate for radiation-induced hereditary disorders is 0.6 × 10−2 per sievert (that is, 0.6 percent per sievert). By way of comparison, it is estimated that the natural spontaneous mutation rate in humans is approximately 10 percent.} \tn 
% Row Count 29 (+ 8)
\hhline{>{\arrayrulecolor{DarkBackground}}--}
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\mymulticolumn{2}{x{5.377cm}}{\bf\textcolor{white}{Effect of Radiation on the Embryo and Foetus}}  \tn
% Row 0
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{Although the increased risk of cancer-induction is of concern, the possibility of developmental effects is equally important.} \tn 
% Row Count 3 (+ 3)
% Row 1
\SetRowColor{white}
\mymulticolumn{2}{x{5.377cm}}{{\bf{Experiments in Animals}}} \tn 
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% Row 2
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\mymulticolumn{2}{x{5.377cm}}{It is clear that moderate doses of radiation can have an enormous effect on the developing embryo.} \tn 
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% Row 3
\SetRowColor{white}
\mymulticolumn{2}{x{5.377cm}}{The principal factors are the dose, dose rate and the stage of gestation. Most data have been obtained from experimental animals, predominantly mouse, where we have:} \tn 
% Row Count 10 (+ 4)
% Row 4
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{1. reproduction in quantity;} \tn 
% Row Count 11 (+ 1)
% Row 5
\SetRowColor{white}
\mymulticolumn{2}{x{5.377cm}}{2. relatively short gestation periods;} \tn 
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% Row 6
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\mymulticolumn{2}{x{5.377cm}}{3. accurate radiation doses; and} \tn 
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% Row 7
\SetRowColor{white}
\mymulticolumn{2}{x{5.377cm}}{4. specific times of conception.} \tn 
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% Row 8
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{The in utero development period can be accurately divided into three stages; namely preimplantation, organogenesis and the foetal stage.} \tn 
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% Row 9
\SetRowColor{white}
\mymulticolumn{2}{x{5.377cm}}{{\bf{Preimplantation}}: he time from fertilisation to when the embryo attaches to the wall of the uterus.} \tn 
% Row Count 20 (+ 3)
% Row 10
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{It is the most sensitive stage for lethal effects of radiation.} \tn 
% Row Count 22 (+ 2)
% Row 11
\SetRowColor{white}
\mymulticolumn{2}{x{5.377cm}}{However, during the first few divisions the cells are undifferentiated and lack predetermination for a particular organ system. If radiation were to kill some cells at this stage, the remaining cells could survive and continue the embryonic reproduction normally; the only effect would be a delay in development.} \tn 
% Row Count 29 (+ 7)
% Row 12
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{Consequently, there is either a radiation-induced spontaneous abortion (if all cells are killed) or the embryo survives and grows normally in utero and afterwards (if at least one cell survives). This is referred to as an all-or-nothing effect.} \tn 
% Row Count 34 (+ 5)
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\vfill
\columnbreak
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\mymulticolumn{2}{x{5.377cm}}{\bf\textcolor{white}{Effect of Radiation on the Embryo and Foetus (cont)}}  \tn
% Row 13
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{{\bf{Organogenesis}}: period during which the major organs are developed.} \tn 
% Row Count 2 (+ 2)
% Row 14
\SetRowColor{white}
\mymulticolumn{2}{x{5.377cm}}{The principal effect of radiation is the production of a variety of congenital abnormalities of a structural nature.} \tn 
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% Row 15
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{{\bf{The Foetal Stage}}: the growth of the structures already formed takes place.} \tn 
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% Row 16
\SetRowColor{white}
\mymulticolumn{2}{x{5.377cm}}{Functional changes have been observed on the haematopoietic system, liver, kidney and gonads following irradiation. Much higher doses of radiation are required to produce death during this period than at other stages of development.} \tn 
% Row Count 12 (+ 5)
% Row 17
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{{\bf{Experience in Humans }}} \tn 
% Row Count 13 (+ 1)
% Row 18
\SetRowColor{white}
\mymulticolumn{2}{x{5.377cm}}{Once again, our knowledge mainly comes from studies of bomb survivors and from early medical exposures which were mainly therapeutic irradiations.} \tn 
% Row Count 16 (+ 3)
% Row 19
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{At any given time, there will be a certain percentage of the female population who are pregnant. From a statistical point of view, the stage of these pregnancies should be distributed roughly uniformly throughout the typical nine-month gestation period.} \tn 
% Row Count 22 (+ 6)
% Row 20
\SetRowColor{white}
\mymulticolumn{2}{x{5.377cm}}{Consequently, there ought to be approximately as many females who are only one day pregnant, or who are 100 days pregnant, or who are just one day from giving birth, etcetera.} \tn 
% Row Count 26 (+ 4)
% Row 21
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{In the bomb survivors who were irradiated in utero, too few persons have been identified who were younger than four weeks gestational age at the time the bomb was dropped. Additionally, no birth defects were found as a result of irradiation before 15 days of gestational age.} \tn 
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\mymulticolumn{2}{x{5.377cm}}{\bf\textcolor{white}{Effect of Radiation on the Embryo and Foetus (cont)}}  \tn
% Row 22
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{These results are consistent with animal experiments which demonstrated the 'all-or-nothing effect', that is, either death of the embryo or normal development.} \tn 
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% Row 23
\SetRowColor{white}
\mymulticolumn{2}{x{5.377cm}}{In humans, the principal effects of irradiation in utero are small head size (microcephaly) and mental retardation.} \tn 
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% Row 24
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{These results are ultimately used to extrapolate to very low doses to give recommendations regarding dose limits for radiation workers (female) and the role of radiation tests in pregnancy.} \tn 
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\hhline{>{\arrayrulecolor{DarkBackground}}--}
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\mymulticolumn{2}{x{5.377cm}}{\bf\textcolor{white}{Exposure to Medical Radiation}}  \tn
% Row 0
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{In humans, the relationship between microcephaly and x-irradiation of the pelvis was recognised from early radiation therapy experience. Additionally, several other defects were also reported and although the number of cases studied is small and the radiation doses not known with any certainty.} \tn 
% Row Count 6 (+ 6)
% Row 1
\SetRowColor{white}
\mymulticolumn{2}{x{5.377cm}}{{\bf{Cancer in childhood after irradiation in utero}}} \tn 
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% Row 2
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{An association between exposure to diagnostic irradiation in utero and the subsequent development of childhood cancer or leukaemia has been suggested.} \tn 
% Row Count 10 (+ 3)
% Row 3
\SetRowColor{white}
\mymulticolumn{2}{x{5.377cm}}{Several investigations have demonstrated a very slight increase in cancer incidence in children exposed to radiation.} \tn 
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% Row 4
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{Of 7649 children who developed leukaemia or cancer, 1141 had been irradiated in utero, whereas in an identical number of control children (no cancer) only 774 had been irradiated in utero.} \tn 
% Row Count 17 (+ 4)
% Row 5
\SetRowColor{white}
\mymulticolumn{2}{x{5.377cm}}{Although this suggests an association between irradiation and childhood cancer, you can see that this study also provides conflicting results. For example, many children (6508 in fact) who did develop cancer had not been irradiated in utero and 774 who had been irradiated did not develop cancer. Consequently, these results and others have stirred lengthy debate about whether or not the relationship is one of cause and effect, or simply a correlation dependent on other health-related issues.} \tn 
% Row Count 27 (+ 10)
% Row 6
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{Although, this debate is still ongoing it is obvious that careful consideration must be given to evaluate the possible benefits versus the potential risks involved in any radiological procedure involving foetal irradiation.} \tn 
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\hhline{>{\arrayrulecolor{DarkBackground}}--}
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\mymulticolumn{2}{x{5.377cm}}{\bf\textcolor{white}{Factors Influencing Effects and Risks}}  \tn
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\mymulticolumn{2}{x{5.377cm}}{{\bf{Dose}}} \tn 
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% Row 1
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\mymulticolumn{2}{x{5.377cm}}{The amount of dose delivered is also important in determining the likelihood and severity of effects. At doses under 0.1 Gy there is unlikely to be any significant effect on organogenesis or foetal development as the threshold for these problems is not reached.} \tn 
% Row Count 7 (+ 6)
% Row 2
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{hen doses climb above this level in the organogenesis period, it is recommended that women be councilled over the potential for congenital abnormalities induced by radiation.} \tn 
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% Row 3
\SetRowColor{white}
\mymulticolumn{2}{x{5.377cm}}{Depending on your religious or ethical viewpoints, it is also recommended that therapeutic abortion of the pregnancy be discussed with women who are irradiated in the organogenesis period.} \tn 
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% Row 4
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{The likelihood of stochastic effects is related to the exposed dose in a linear fashion.} \tn 
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% Row 5
\SetRowColor{white}
\mymulticolumn{2}{x{5.377cm}}{{\bf{Limits of data on humans}}} \tn 
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% Row 6
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{There is no evidence in humans that radiation increases the rate of death during the implantation period. This data must be interpreted from animal studies.} \tn 
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% Row 7
\SetRowColor{white}
\mymulticolumn{2}{x{5.377cm}}{There is no compelling evidence that exposure during organogenesis leads to significant abnormalities from human studies. Data is interpreted from animal studies.} \tn 
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% Row 8
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{Data on exposures after embryogenesis is limited to survivors of the atomic bombs; and is limited to evidence of microcephaly and mental retardation.} \tn 
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% Row 9
\SetRowColor{white}
\mymulticolumn{2}{x{5.377cm}}{{\bf{Gestational Age}}} \tn 
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\mymulticolumn{2}{x{5.377cm}}{\bf\textcolor{white}{Factors Influencing Effects and Risks (cont)}}  \tn
% Row 10
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{The gestational age is the most important factor in determining what kind of effect will occur.} \tn 
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% Row 11
\SetRowColor{white}
\mymulticolumn{2}{x{5.377cm}}{Before implantation has occurred, the most likely effects are loss of the embryo (dose dependent) or no effect. It seems that the cells at the preimplantation stage are capable of differentiating into any of the required cells for development to occur, and the loss of a significant number of these cells leads to demise of the embryo.} \tn 
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% Row 12
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{Organogenesis occurs between implantation and the commencement of the foetal stage. During this period the precursors of all major organs are formed. Damage to these prognenitor cells may lead to severe development abnormalities (such as failure of organ formation or structural defects).} \tn 
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% Row 13
\SetRowColor{white}
\mymulticolumn{2}{x{5.377cm}}{The foetal stage (from about 6 weeks after conception) is more resistant to serious abnormalities or prenatal death. Animal studies suggest a high rate of growth retardation. Human evidence suggests microcephaly, growth retardation and mental retardation are more common, particularly in the early foetal period.} \tn 
% Row Count 22 (+ 7)
% Row 14
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{Irradiation in all periods can increase the rate of childhood cancer, which is more dose dependent.} \tn 
% Row Count 24 (+ 2)
\hhline{>{\arrayrulecolor{DarkBackground}}--}
\end{tabularx}
\par\addvspace{1.3em}

\begin{tabularx}{5.377cm}{p{0.4977 cm} p{0.4977 cm} }
\SetRowColor{DarkBackground}
\mymulticolumn{2}{x{5.377cm}}{\bf\textcolor{white}{Pregnancy and the Radiation Worker}}  \tn
% Row 0
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{Once pregnancy has been declared, the conceptus should be protected by applying a supplementary equivalent-dose limit to the surface of the worker's abdomen of 2 mSv for the remainder of the pregnancy.} \tn 
% Row Count 5 (+ 5)
% Row 1
\SetRowColor{white}
\mymulticolumn{2}{x{5.377cm}}{This will ensure that the foetus does not receive a dose in excess of the 1 mSv limit applicable to members of the general public.} \tn 
% Row Count 8 (+ 3)
% Row 2
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{Typically, the annual occupational radiation dose received by radiation therapy technologists is of the order of 200 µSv. Consequently, there is usually no reason from a radiation safety point of view that should restrict such a person from working until the full term of the pregnancy} \tn 
% Row Count 14 (+ 6)
% Row 3
\SetRowColor{white}
\mymulticolumn{2}{x{5.377cm}}{However, it is appropriate that the pregnant worker be excluded from any employment activity that carries a significant probability of high accidental doses.} \tn 
% Row Count 18 (+ 4)
% Row 4
\SetRowColor{LightBackground}
\mymulticolumn{2}{x{5.377cm}}{For example, radiation workers would routinely be excluded from high-dose brachytherapy applications, fluoroscopy and radiopharmaceuticals work.} \tn 
% Row Count 21 (+ 3)
% Row 5
\SetRowColor{white}
\mymulticolumn{2}{x{5.377cm}}{In terms of radiation protection, a second badge dosimeter for the abdomen needs to be issued, and the two badges need to be checked on a monthly basis (instead of once every 3 months) throughout the term of pregnancy. Lead abdomen shielding is also available for a pregnant radiation worker.} \tn 
% Row Count 27 (+ 6)
\hhline{>{\arrayrulecolor{DarkBackground}}--}
\end{tabularx}
\par\addvspace{1.3em}


% That's all folks
\end{multicols*}

\end{document}