Radiobiology Unit 6 Late Effects Of Radiation

Front 1

BEIR V 1990 Committee on the Biological Effects of Radiation

Back 1

Follow up of A-bomb survivors indicates that the number of excess cancers increase with age. This is in agreement with the relative risk model.

Front 2

Estimates are still uncertain for A-bomb survivors. One reason is because the population exposed is just now entering the age where cancers are most prevalent.

Back 2

There were about 76,000 survivors for whom dose estimates are available and who have been traced through 1985. However, almost half of these people received doses less than 0.5 rem.

Front 3

Various studies on the survivors of Hiroshima and Nagasaki show that a population exposed to a dose of 12.5 Rem will have a measurable

Back 3

increase about 1% in the incidence of cancer.

Front 4

Note that the measurements are made on a population, not on individuals.

Back 4

We can never say that a particular individual exposed to a particular dose of radiation will develop cancer.

Front 5

BEIR V reported that the risk for solid tumors is 3 times larger than that reported in the BEIR III report

Back 5

and 4 times larger for leukemias.

Front 6

This change was mostly due to new dosimetry measurements which showed that the neutron component of the dose

Back 6

was much smaller than previous estimates.

Front 7

RBE for neutrons is high. So the result is that survivors received less

Back 7

biologically effective dose than was previously estimated.
LESS ACTUAL DOSE CAUSING THE SAME OBSERVED HEALTH EFFECTS.

Front 8

According to BEIR V

Back 8

If 100,000 people of all ages are exposed to 0.1 Gy or 10 rads in a single brief exposure, about 800 extra cancer deaths would be expected to occur during their remaining lifetimes.

Front 9

According to BEIR V cont.

Back 9

This is in addition to the 20,000 cancer deaths that would occur in the absence of the radiation.

Front 10

According to BEIR V cont. 2

Back 10

For all cancer other than leukemia, the study showed that under 4 Gray of exposure, the linear model for risk fit most closely. For leukemia, the linear quadratic model was more appropriate.

Front 11

Using a linear model, how many extra deaths would be expected for the same population to 1 Rem of radiation?

Back 11

80 extra cases
This result in an increase of 20000/20080 = 0.4% difficult to measure

Front 12

BEIR VI 1999 Committee on the Biological Effects of Radiation

Back 12

This was the last BIER report to be published the National Research Council

Front 13

BEIR VI 1999 Committee on the Biological Effects of Radiation cont.

Back 13

The motivation for this report was not A-bomb survivors but the health effects of radon, specifically, lung cancers caused by radon and radon daughters in Private Homes

Front 14

The study extrapolated data from miners, who receive on average a much larger dose than people do from household radon.

Back 14

The study was also complicated by by other hazardous exposures common to miners.

Front 15

Despite that radon is one of the most extensively studied carcinogens, the conclusion of the report is that it is inconclusive.

Back 15

There is no definite answer regarding radon and lung cancer, probably because the risk is low. CIgarette smoke is for more dangerous by comparison.

Front 16

The best estimate was that of the 11,000 lung caner deaths per year is non smokers, 2100 to 2900 are

Back 16

radon related lung cancers

Front 17

There is also evidence of a synergistic effect between radon and smoking. That is the two combined are more hazardous than each individually.

Back 17

That is the two combined are more hazardous than each individually.

Front 18

Local Tissue Damage - Early

Back 18

Skin is a radiosensitive organ because it is a continually renewing system of cells. About 2% of skin cells are replaced each day. Damage to the basal cells of skin is most common as they are the most radioactive skin type cells,

Front 19

A single dose of 100 to 300 rads can cause skin reddening called

Back 19

erythema, which is similar to a sunburn. The erythema, appears in 1-2 days after irradiation. With an increased dose or moist desquamation will occur.

Front 20

Radiation effects on the skin are a threshold effect. No effect is seen at low doses.

Back 20

There is a minimum amount of radiation required about 50 rads before any effect is seen

Front 21

Local Tissue Damage - Late

Back 21

Late changes to skin from radiation include atrophy, fibrosis, changes in pigmentation, necrosis, ulceration and permanent depilation ( loss of hair.)

Front 22

PICS

Back 22

See P.P

Front 23

A dose about 10 rads is required for any measurable change in humans. 10 rads can produce a measurable decrease in circulating

Back 23

WBC, a decrease in the sperm count, and can suppress and delay menstruation in females.

Front 24

Non-Specific Life Shortening ( Does Not Happen!!!)

Back 24

Previous studies from the 50's and 60's showed that animals which were exposed to radiation insufficient to cause death, recovered but died sooner.

Front 25

Additional studies have shown that at low doses, early death was due to

Back 25

neoplasms (cancer)

Front 26

Studies of humans, specifically A-bomb survivors who did not die from caner,

Back 26

do not show acceleration of non-specific aging from radiation exposure.

Front 27

Late Effects of Radiation: Genetic Changes

Back 27

Radiation can effect the reproductive cells of humans, It does this in two ways:

Front 28

1. With sufficient radiation, the cell will be killed.

Back 28

2. If the cell is not killed, it may cause a hereditary change which can be carried to the next generation.

Front 29

Male Sterility

Sperm Development

Back 29

Primary Spermatocytes -> secondary spermatocytes-> spermatids-> spermatoza

Front 30

Radio-resistance increases with each cell type leading

Back 30

to the mature spermatozoa (adult sperm cell)

Front 31

Because of this, sterility from radiation exposure is delayed. The individual remains fertile until all the mature sperm are used up.

Back 31

Stems cells are killed, so there are no cells to replace them.

Front 32

Radiation Induced Sterility - Males

Back 32

250 rads may cause temporary sterility in males lasting 1-2 years, but as little as 15 rads may cause temporary sterility.

Front 33

Radiation Induced Sterility - Males cont.

Back 33

350-600 rads acute exposure is enough to cause permanent sterility in males.

Front 34

Female Sterility

Back 34

Production of reproduction cells is different. There are no stem cells, but there are three types of immature eggs cells.

Front 35

A dose of 50 rads

Back 35

may cause temporary sterility in females.

Front 36

A dose of at least 250 to 600 rads

Back 36

can cause permanent sterility in females.

Front 37

Radiation does not produce bizarre mutations!

Back 37

Radiation produces an increase in the frequency of those mutations which occur spontaneously in any species.

Front 38

No threshold for mutations:

Back 38

Any amount of radiation carries some small risk of mutation

Front 39

No threshold for mutations: cont

Back 39

Most mutations whether spontaneous or induced by radiation are harmful to the organism.

Front 40

aka epithalamus, secretes melantonin (circadian rhythms)

Back 40

pineal gland-roof of the 3rd ventricle

Front 41

Risk estimates developed from mouse experiments appear to be

Back 41

similar to the genetic risk for humans.

Front 42

Categorizing Mutations

Mendelian Diseases

Back 42

Caused by a single genetic mutation and show a simple predictable pattern.

Front 43

Chromosomal Mutations

Back 43

Are caused by gross abnormalities in he number of chromosomes i.e down's syndrome is caused by an extra chromosome 21

Front 44

Categorizing Mutations

Multifactorial Diseases

Back 44

Describes the conditions which have a genetic component but not follow a simple mendelian patten.
Influenced by both genetics, environment & behavior. Ex. heart disease, diabetes, autism

Front 45

A parameter known as the doubling dose =

Back 45

is used in genetic experiments. It is the amount of radiation required to produce twice the amount spontaneous mutations seen in the population.

Front 46

The Mega Mouse Project

Back 46

Used about 7 million mice to study the effects of radiation. Information on genetics defects comes almost entirely from animal studies.

Front 47

Summary Findings

1. Different mutations have different radio sensitivities

Back 47

Radiosensitivity can differ by a factor of 35

Front 48

2. There is a dose rate effect for mutations

Back 48

in mice. Fewer mutation at low doses. At low doses the mutations rate in female reproductive cells is not above that of an un-irradiated mice.

Front 49

3. Male Mice are more radiosenitive than females.

Back 49

At a low dose rate, the male mice carries practically all of the burden of genetic mutation.

Front 50

4. Genetic consequences following irradiation are reduced if there is

Back 50

time between irradiation and conception. This may indicate a repair process. 6 months is the minimum recommended delay for humans.

Front 51

5. BEIR V sys that the doubling doe for humans

Back 51

is not likely to be less than 100 rem, estimated from mice,
The doubling dose for mice was found to be about 30 rads.