Lecture 12 - Pennsylvania State Universitypersonal.psu.edu/mxs43/472/lecture12.pdf · 2018-09-25 · Lecture 12 Thursday, February 23, 17. ... Inversion Activation of an oncogene

Sources of natural radiation, effects of high doses of radiation, and effects of low doses.

Lecture 12

Thursday, February 23, 17

Summary/implications of several points we discussed concerning effects of radiation:

Principal hazards of ionizing radiation:

(a) genetic effects, (b) carcinogenic effects (effects on the development of embryo / fetus).

Radiation and Cancer.Radiation does cause cancer, some mechanisms are

understood. However the full picture is very unclear.

Ionization radiation is quite efficient at inducing chromosome aberrations such as

deletions and translocations


Links betweenchromosomal aberrations and cancer

Deletion Loss of tumor suppressor gene

Translocation or

Inversion

Activation of an oncogene or

creation of fusion gene


Before switching to application of particle beams in oncologic treatments we will consider effects of low and high doses of radiation on human bodies.

Human exposure

Effects of low doses of radiation

High doses.


Sources of radiation


The equivalent dose to a tissue is found by multiplying the absorbed dose, in grays, by a dimensionless "quality factor" Q, dependent upon radiation type, and by another dimensionless factor N, dependent on all other pertinent factors. N depends upon the part of the body irradiated, the time and volume over which the dose was spread, even the species of the subject. Together, Q and N constitute the radiation weighting factor, rW. For an organism composed of multiple tissue types a weighted sum or integral is often used.

Relevant Quantities & Units – for Individuals

UNITSQUANTITY DEFINITION New Old

Absorbed Dose Energy per unit mass Gray (Gy) rad

Equivalent Dose Average dose X radiation Sievert (Sv) rem weighting factor

Effective Dose Sum of equivalent doses to Sievert rem organs and tissues exposed, each multiplied by the appro- priate tissue weighting factor

Committed Equivalent dose integrated Sievert remEquivalent Dose over 50 years (relevant to incorporated radionuclides)

Gy=100 rad, Sv=100 rem.


http://en.wikipedia.org/wiki/Dimensionless

http://en.wikipedia.org/wiki/Dimensionless

http://en.wikipedia.org/wiki/Weighted_sum

http://en.wikipedia.org/wiki/Weighted_sum

http://en.wikipedia.org/wiki/Integral

http://en.wikipedia.org/wiki/Integral

Natural sources - USTotal 3.0mSv/year

Cosmic rays 10%; Terrestrial 10%, Internal 13%, radon 67%

Europe


70 mrem/yr

Medical procedures 53 mremsConsumer products 10 mremsOne coast to coast airplane flight 2 mremsWatching color TV 1 mremSleeping with another person 1 mremWeapons test fallout less that 1 mremNuclear industry less than 1 mrem

Normal annual exposure from man-made radiation

Normal annual exposure from natural radiation

300 mrem/year§ Radon gas 200 mrem§ Human body 40 mrem § Rocks, soil 28 mrem§ Cosmic rays 27 mrem


Exposure at Different Elevations

020406080

100120140

Sea Level Death Valley Richland Denver Ledville

1 mrem/year = 200 feet of altitude 4 mrem/year = 800 feet500 mrem/year = some isolated populations


Cosmic rays (CR)Intergalactic CR, Solar CRs. Produce

activated nuclei 3H, 7Be, 14C, ...

1000 h /year (pilots) = 5 mSv


Terrestrial


Internal - our body is Radioactive - food, air, radiation.

Main components: 40K, 14C.

7000 decays/second in an adult.


Most exposure to radiation is at very low levels of radiation

0

5000

10000

15000

20000

25000

No cancer detected below this level Occupational exposure limit Ave background Population Exposure limit

mre

ms


Health effects cannot be seen at low levels of radiation

0

1000

2000

3000

4000

5000

6000

Occupational exposure limit Average background Population exposure limit

mre

ms


Background Cancer

Over 30 % of us will develop cancer About 25 % will die of cancer

Cancer is variable as a function of • Genetic Background• Environmental Exposures

• Diet• Lifestyle



Problems estimating cancer risks

Dose, Statistics, Control, Latency, Dose extrapolation, Dose rate extrapolation, Age and time dependencies,

neutrons in Hiroshima.

The BIG caveat:Radiation risk estimates at low doses are based on

plausible assumptions, but are estimates nevertheless.

They are not, and can never be, direct measurements!



Some new studies suggest approach from above. There are also claims of a negative

correlation for small doses.






Longevity of A-bomb Survivors




Lifetime cancer mortality risk as a function of age at exposure

For children the variation of sensitivity to radiation induced

cancer is so great that three age ranges are

justified0-5 years

6-18 years>18 years


Radiation-Induced Mutations

Radiation does not produce new, unique mutations, but simply increases the incidence of the same mutations that occur spontaneously



Heritable Effects

Children of the survivors of the A-bomb attacks have been studied for:

Untoward pregnancy outcome

Death of live-born children

Sex chromosome abnormalities

Electrophoretic variants of blood proteins

But no statistically significant effects have been observed


Factors Influencing Probabilityof Teratogenic Effects

Dose to embryo / fetus

Stage of gestation at time of exposure


A-bomb survivors irradiated in-uteri, with microcephaly


Microcephaly at Hiroshima

Dose (rad)

Incidence of microcephaly for exposure during 6 to 11 weeks gestation period

Incidence of microcephaly for exposure during 6 to 11 weeks gestation period

0 4% 31/7641-9 11% 2/19

10-19 17% 4/2420-29 30% 3/1030-39 40% 4/10

50-99 70% 7/10

100 100% 7/7


Radiation and Cancer

Can low-dose risks be estimated directly from groups exposed to low doses of

radiation?

Recent study of 120,000 nuclear workers exposed to –40 mSv consistent both with:

• Zero risk

• A risk appropriately extrapolated from A-bomb survivor data.


Other studies: miners (exposed to higher levels of radon than in houses) - positive correlation, comparisons of cancer - vs radon concentration in houses- no positive correlation. Possible difference - A-bomb high flux & short time; others small flux over long period of time.

Lung -cancermortality vs level of radon.


Is it possible that low level radiation is beneficial?dependence on the dose for very small doses seems to be not linear

1. Super-low doses - hyperradiosensitivity

1I. Somewhat higher low doses - radiation hormesis (hormesis is a nonspecific effect of an agent at low doses or concentrations on a living organism, which causes changes diametrically opposite to the damaging effect of high doses of the same agent). Adaptive response?

NBR = normal background

radiation

Doses below NBR also appears to produce negative effect - body is adopted to function optimally at the radiation level ~NBR!!!


Problem: observing effect on the level of A-bomb exposure is practically impossible. On the other hand this is a level of CAT scans (they are not the whole body). Need to minimize the level.

Example: Lifetime attributable cancer mortality risk, as a function of age at exam, for a single CT examination

0 10 20 30 40 50 60 70 80

Age at CT Examination (Years)

Estimated Lifetim

e Attributable R

isk (%)

AbdominalHead

0.00

0.05

0.10

0.15200 mAs


Acute effects of the whole body radiation


LD50/30 50% mortality in 30 days.


I do not have time/desire to show and comment on theseveral recent cases of high exposure as presented in the file wholebody.ppt which I found on the web. I will put it to the 472 directory.


Documents

Lecture 12 - Pennsylvania State Universitypersonal.psu.edu/mxs43/472/lecture12.pdf · 2018-09-25 · Lecture 12 Thursday, February 23, 17. ... Inversion Activation of an oncogene