17. Chromosomal deletions

18. Chromosomal translocations

21. Outcomes after cell exposure
DAMAGE TO DNA
DAMAGE REPAIRED
CELL NECROSIS OR
APOPTOSIS
TRANSFORMED
CELL

22. Normal human
lymphocyte:
chromosomes
uniformly
distributed

23. Apoptotic cell:
chromosomes
and nucleus
fragmented
and collapsed
into apoptotic
bodies

25. Effects of cell death

26. Coronary angioplasty twice in a day followed by bypass graft because of complication. Dose  20 Gy (ICRP 85)
(a) 6-8 weeks after multiple coronary angiography and angioplasty procedures.
(b) weeks
(c) months after the procedures showing tissue necrosis .
(d) Close-up photograph of the lesion shown in (c).
(e) Photograph after skin grafting. (Photographs courtesy of T. Shope & ICRP).

28. Biological effects of ionizing radiation
Deterministic
e.g. Lens opacities, skin injuries,
infertility, epilation, etc
Stochastic
Cancer, genetic effects.

29. Threshold Doses for Deterministic Effects
Cataracts of the lens of the eye Gy
Permanent sterility
males Gy
females Gy
Temporary sterility
males Gy
females Gy
Severity of
effect
dose
threshold

31. Whole body response: adult2 1
Acute irradiation syndrome
Chronic irradiation syndrome
Steps:
Prodromic (onset of disease)
Latency
Manifestation
1-10 Gy
Whole body clinic of a partial-body irradiation
Mechanism: Neurovegetative disorder
Similar to a sick feeling
Quite frequent in fractionated radiotherapy Gy
> 50 Gy
Survival time
BONE MARROW
GASTRO
INTESTINAL
Lethal dose 50 / 30
CNS
(central nervous system)
Dose

32. Lethal dose 50 / 30
“Dose which would cause death to 50% of the population in 30 days”.
Its value is about 2-3 Gy for humans for whole body irradiation.

36. Timing of events leading to radiation effects.
-15
Energy deposition 10
Excitation/ionization
PHYSICAL INTERACTIONS
-12
Initial particle tracks 10
Radical formation -9 10
Diffusion, chemical reactions
PHYSICO-CHEMICAL INTERACTIONS -6
Initial DNA damage 10 ) c e s ( E -3 10
1 ms
DNA breaks / base damage M I T 10
1 second
Repair processes
Timing of events leading to radiation effects.
Damage fixation 3
BIOLOGICAL RESPONSE 10
1 hour
Cell killing
1 day
Mutations/transformations/aberrations 6 10
Proliferation of "damaged" cells
1 year
Promotion/completion 10 9
Teratogenesis
MEDICAL EFFECTS
Cancer
100 years
Hereditary defects

37. Radiosensitivity [RS] (1)
RS = Probability of a cell, tissue or organ of suffering an effect per unit of dose.
Bergonie and Tribondeau (1906): “RS LAWS”: RS will be greater if the cell:
Is highly mitotic.
Is undifferentiated.
Has a high cariocinetic future.

38. Radiosensitivity (2) High RS Medium RS Low RS Bone Marrow Spleen
Thymus
Lymphatic nodes
Gonads
Eye lens
Lymphocytes (exception to the RS laws)
Skin
Mesoderm organs (liver, heart, lungs…)
Muscle
Bones
Nervous system

39. Factors affecting the radiosensitivity
Physical
LET (linear energy transfer):  RS
Dose rate:  RS
Chemical
Increase RS: OXYGEN, cytotoxic drugs.
Decrease RS: SULFURE (cys, cysteamine…)
Biological
Cycle status:
 RS: G2, M
 RS: S
Repair of damage (sub-lethal damage may be repaired e.g. fractionated dose)
% survivor cells
 LET
 LET G0 M M M G2 G1 S

40. Systemic effects Which Organ How much Dose
Effects may be morphological and/or functional
Factors:
Which Organ
How much Dose
Effects
Immediate (usually reversible): < 6 months e.g.: inflammation, bleeding.
Delayed (usually irreversible): > 6 months e.g.: atrophy, sclerosis, fibrosis.
Categorization of dose
< 1 Gy: LOW DOSE
1-10 Gy: MODERATE DOSE
> 10 Gy: HIGH DOSE
Regeneration means replacement by the original tissue while Repair means replacement by connective tissue.

41. Skin effects
Following the RS laws (Bergonie and Tribondeau), the most RS cells are those from the basal stratum of the epidermis.
Effects are:
Erythema: 1 to 24 hours after irradiation of about 3-5 Gy
Alopecia(*): 5 Gy is reversible; 20 Gy is irreversible.
Pigmentation: Reversible, appears 8 days after irradiation.
Dry or moist desquamation: traduces epidermal hypoplasia (dose  20 Gy).
Delayed effects: teleangiectasia (**), fibrosis.
Histologic view of the skin
From “Atlas de Histologia...”. J. Boya
Basal stratum cells, highly mitotic, some of them with melanin, responsible of pigmentation.
(*):alopecia: loss or absence of hair
(**): ectasia: swelling of part of the body

42. Skin reactions Threshold Weeks to Injury Dose to Onset Skin (Sv)
Early transient erythema 2
<<1
Temporary epilation 3 3
Main erythema 6
1.5
Permanent epilation 7 3
Dry desquamation 10 4
Skin damage
from prolonged
fluoroscopic
exposure
Invasive fibrosis 10
Dermal atrophy 11
>14
Telangiectasis 12
>52
Moist desquamation 15 4
Late erythema 15
6-10
Dermal necrosis 18
>10
Secondary ulceration 20
>6

43. Skin injuries

44. Skin injuries

45. Sv single brief exposure
Effects in eye
Eye lens is highly RS.
Coagulation of proteins occur with doses greater than 2 Gy.
There are 2 basic effects:
Histologic view of eye:
Effect
Sv single brief exposure
Sv/year for many years
Detectable opacities
> 0.1
From “Atlas de Histologia...”. J. Boya
Eye lens is highly RS, moreover, it is surrounded by highly RS cuboid cells.
Visual impairment (cataract)
5.0
> 0.15

46. Eye injuries

48. Effects of antenatal exposure (1)
As post-conception time increases RS decreases
It is not easy to establish a cause-effect relation because there are a lot of teratogenic agents, effects are unspecific and not unique to radiation.
There are 3 kinds of effects: lethality, congenital anomalies and large delay effects (cancer and hereditary effects).
Congenital anomalies %
Lethality
Pre-implantation
Organogenesis
Foetus
Time

49. Effects of antenatal exposure (2)
Lethal effects can be induced by relatively small doses (such as 0.1 Gy) before or immediately after implantation of the embryo into the uterine wall. They may also be induced after higher doses during all the stages during intra-uterine development.
0.1 Gy %
Lethality
Time
Pre-implantation
Organogenesis
Foetus

50. Effects of antenatal exposure (3)
Mental retardation:
ICRP establishes that mental retardation can be induced by radiation (Intelligence Quotient score < 100).
It occurs during the most RS period: 8-25 week of pregnancy.
Risks of antenatal exposure related to mental retardation are:
8-15 week
15-25 week
Severe mental retardation with a risk factor of 0.4/Sv
Severe mental retardation with a risk factor of 0.1/Sv

51. Delayed effects of radiation
Classification:
SOMATIC: they affect the health of the irradiated person. They are mainly different kinds of cancer (leukemia is the most common, with a delay period of 2-5 years, but also colon, lung, stomach cancer…)
GENETIC: they affect the health of the offspring of the irradiated person. They are mutations that cause malformation of any kind (such as mongolism)