PCB675 Radiation Biology Hereditary Effects Week 9 Part 2

Hereditary effects. 1. Definition 2. statistic vs normal incidence

1. A hereditary effect refers to a trait, condition, or disease that is passed down genetically from parents to their offspring

2. Multiple sources does not find evidence of statistically significant increases in adverse conditions developed from IR exposure

Stillbirth risks in mothers who had RT before puberty

Possible increased risk of stillbirths and neonatal death of children for mothers who experienced IR pre puberty

Why is hereditary data on IR on humans hard to find? 4 reasons

1. long life cycle

2. few offspring

3. not high enough population in data

4. large incidence of naturally occuring genetic damage unrelated to IR

Animal studies - vinegar fly IR exposure. 3 conclusions

1. No dose threshold

2. Dose/effect has proportional relationship

3. There is no effect of fractionation

Megamouse experiment findings investigating coat, ear colour, and ear deformation genes after IR. 1. Gene loci 2. Soe rate and sex 3. time between irradiation and conception 4. Stage of sex cells irradiated

1. Different gene loci have different rates of induction of mutation

2. Mutation frequency is dose-rate dependent and sex dependent

3. The time between irradiation and conception is important

4. Magnitude of the effect depends upon the stage of sex cell irradiated

1. different gene loci have different rates of induction of mutation

the variation is approx a factor of 35 between the 7 loci studied

Oocyte comparison with spermatogonia

1. At high dose rates (> 1 Gy/min) the spermatogonia and oocytes have a similar sensitivity.

2. As the dose rate decreases to < 10-² Gy/min both the male and female sensitivity decrease BUT

3. The sensitivity of the oocytes decreases far more than that of the spermatogonia

4. At low dose rates the mutation frequency in oocytes (female germ cell) is not distinguishable from the natural incidence even for several Gy

5. Thus at low dose rates all the genetic burden of exposure to IR is carried by the male and

6. on average the Male is more sensitive than the female

Time between irradiation and conception is important

A delay in conception following irradiation significantly reduces the effect - allowing time for cells to repair

In humans a delay of approx 6 months is an assumed safe margin

Stage of sex cells irradiated

The latter stages of the male and female sex cells are more sensitive by approx x5 compared with the early stages

Risk estimates of genetic damage may be expressed in relative terms as (2 terms)

The doubling dose - dose of radiation that doubled spontaneous rate

The number of mutation per million per 10 mSv

Megamouse experiment average relative risk

0.3 x 10-5 mutations /locus/ Gy compared with a spontaneous rate in man of 1 x 10-5 /locus

gives a doubling dose of ~ 3 Gy

Relative estimates for humans

1. Doubling dose is estimated to be 1Gy per generation for low dose rate exposure

2. 30-47 mutations/million births/10mSv of parental exposure in the succeeding generation

3.