PCB675 Week 9 Life Shortening and effects on embryos

Magnitude of radiation life-shortening per Sv (aka radiological ageing)

1-5% reducing in remaining life expectancy per Sv for acute exposure

<1% per Sv for protracted exposure

Life shortening due to radiation is seen in which 2 human populations?

US radiologists

Atomic bomb survivors

‘in-utero effects’ of IR due to radiosensitivity of embyros

Rapid Cell division during gestation in embryos means radiation damage will be seen early as embryos are more radiosensitive.

Three stages of embryonic development

1. The preimplantation stage

2. The organogenesis stage

3. The fetal stage

When is the preimplantation stage, what is the most significant risk to embryo at this stage?

The period from conception until the fertilised egg attaches itself to the wall of the uterus (0-9 days).

Pre-natal (birth) death is most significant risk.

The all or nothing effect of irradiation at the preimplantation stage

Embryos that survive usually develop normally – if the damage is not lethal, the damaged cells are repaired or replaced.

Exception to the all or nothing effect during preimplantation stage

Chromosomal aberration could occur if misrepair occurs – Sensitive stage is 12h after conception (when the two pronuclei fuse to one-cell stage) and Between 30-60 h when the first two cell divisions occur.

What dose can cause cell death in embryos, and the LD50 of preimplantation stage

• A dose as low as 0.05-0.1 Gy can kill (from mouse data) • LD50 is ~ 1 Gy during this stage (data from studies of mice)

Abnormality incidence peak period during organogenesis stage is?

10 days to 6 weeks post conception

How does critical period (aka time of max sensitivity) vary in organogenesis stage of embryonic development?

Sensitive period is different for each organ system.

At which in stage of embryonic development is the CNS most sensitive?

Organogenesis stage

LD50/30 and abnormality dose for organogenesis stage

LD50/30 ~ 1.5 Gy

0.2 Gy can cause an increase in some abnormalities

Possible effects of IR exposure during organogenesis (3)

1. Malformation of organs

2. Small head size

3. Intrauterine growth retardation

What happens to the LD50/30 when irradiation occurs during the late stages of gestation?

Similar to that of new borns (Post natal) in terms of radiosensitivity

What do the symptoms experienced by mice from IR in organogenesis resemble in a human?

Acute radiation syndrome, e.g. the haemopoietic syndrome

Growth retardation, if it occurs, is it permanent or temporary in the live born animal?

may be permanent

Fetal Stage explained 1. what system is affected 2. fetal period is how long? 3. what happens during the whole fetal period?? 4. IS carcinogenesis for women undergoing x-rays stochastic or deterministic? what does it mean for dose threshold.

1. Nervous system may be affected

2. Early Fetal period (weeks 8-16)

3. Throughout whole fetal period

4. Increased carcinogenesis

5. Carcinogenesis observed for women undergoing diagnostic x-ray procedures likely without a dose threshold (i.e. stochastic effect)

Effects of irradiation during organogenesis (primarily to CNS) 1. birth defects 2. growth retardation

1. no birth defects were found (in the A-bomb survivors) as a result of irradiation before 15 days of gestational age

2. However growth retardation was observed (with no catch up growth observed)

Teratogenic effects (congenital disorders) 1. 1. what type of retardation, 2. probability of severe retardation % per Gy 3. normal incidence of mental retardation in the general population, 4. Greatest sensitivity week range, 5. Threshold of mental retardation

1. Mental retardation

2. From A-bomb survivors, the probability of severe retardation is 44% per Gy

3. Compared to 5000/ 10⁶ normal incidence of mental retardation

4. Greatest sensitivity was exposure between 8th and 15th week.

5. There is likely a threshold of ~0.2-0.3 Gy (mental retardation is a deterministic effect)

Teratogenic effects (Congenital disorders) 2. 1. In terms of IQ, 2. IQ decrease per Gy 3. Threshold dose (hint* ans in mGy).

1. Lower IQ

2. Decrease in IQ was dose dependent – about 25 points/Gy.

3. Threshold dose of about 100 mGy, below which the effect was negligible.

Teratogenic effects (congenital disorders) 3. 1. Small head size aka? 2. What happens to those esposed before the 16th week?

1. Microcephaly (small head size)

2. For those exposed before the 16th week, the incidence is proportional to dose from 100-200 mGy til 1.5 Gy (above 1.5 Gy decreased incidence attributed to greater mortality).

Carcinogenic Effects – Childhood cancers. 1. How many cases of death from malignant diseases for children under 10 yrs? 2. obstetric radiography risk of malignancy in childhood, and A bomb contrast.

One of the largest studies (The Oxford Study) considered approx 8,000 cases of death from malignant disease of children < 10 years

Studies show obstetric radiography resulted in an increased risk of malignancy in childhood, but A-bomb survivors data does not support this

Carcinogenic Effects -Childhood cancers. 1. Doll and Wakeford studies suggestion of irradiation risk in utero. 2. Increased risk mGy level and % ERR per Gy after mGy threshold.

Doll and Wakeford study concluded irradiation in utero, especially in the last trimester increases the risk of childhood cancer.

Increased risk starts at about 10 mGy and then ERR is approximately 6% per Gy after that.

Carcinogenic Effects - Lifetime risk of cancers. 1. ICRP 2006

Lifetime risk is elevated

ICRP 2006 considers that it is important to be cautious to assume that lifetime cancer risk following in-utero exposure will be similar to that following irradiation in early childhood,

i.e. at most, about three times that of the population as a whole’.