RAD 315 RADIOBIOLOGY AND RADIATION PROTECTION WHOLE BODY RADIATION

Syndrome Signs and symptoms experienced by irradiated mammal Total body syndrome Radiation syndrome

Acute exposure Given in minutes Total body or almost total body External radiation – penetrating Doses quoted in cGy for x or gamma radiation Lower doses would be needed for same effect if high LET radiation is used

Survival time Is dependent on dose Expressed as mean survival time Varies between species Lethal dose: LD x/z is the dose needed to kill x% in z number of days Females are more resistant Very young and very old are more sensitive

LD50/30 for different species Human ------------- 250 – 300 cGy Monkey------------- 400 Dog ----------------- 300 Rabbit -------------- 800 Rat/mouse -------- 900 Frog ----------------- 700 Goldfish ------------- 2000

Data Has been established from: Animal experiments Hiroshima and Nagasaki Marshall Island fallout Nuclear accidents Medical exposure

Total body exposure After total body exposure, the animal exhibits three main stages of response: Prodromal Latent manifest

prodromal the early symptoms that occur initially after exposure. Occurs for minutes to days Nausea, vomiting, diarrhea Severe PRS usually means poor survival

Latent Occurs for hours to weeks after exposure No major symptoms (latent)

Manifest illness Hours to weeks after exposure Symptoms reflect the systems of the body that has been damaged

Body systems affected There are three body systems affected: Bone marrow GI CNS So there are basically three types of death at three different levels, depending on dose Each has its own PRS

Survival time See graph page 139 Derived from experiments with a variety of species Is dose dependent between 2 – 10 Gy and after 100 Gy Not dose dependent between 10 – 100 Gy There is overlapping of syndromes present after exposure. Table shows PRIMARY cause of death.

Los Alamos in 1958 Major accidental exposure to an individual 3900 – 4900 cGY from neutrons and gamma rays Immediate shock and loss of consciousness No lymphocytes after 8 hours Dead in 35 hours.

CNS syndrome Death occurs within hours as a result of neurological and cardiovascular breakdown. Associated dose: > 5,000 cGy PRS : Immediate diarrhea Fever Hypertension Loss of consciousness

CNS syndrome Manifest symptoms: Disorientation Loss of coordination Respiratory distress Diarrhea Seizures coma

CNS syndrome Prognosis: two days at most Person does not live long enough to get GI and bone marrow symptoms

GI syndrome Prior to Chernobyl, little was known about GI syndrome Death occurs in matter of days due to destruction of intestinal mucosa. Associated dose: 1000 cGy Threshold dose: 600cGy (LD100 = 600 to 1000 cGy)

GI syndrome PRS: N, V, D Manifest Symptoms: Prognosis: about 10 days Dehydration Weight loss exhaustion Prognosis: about 10 days

Bone Marrow Syndrome Possible death due to damage of blood forming organs (bone marrow) Associated dose: 250 to 500 cGy PRS: N, V, fatigue

Bone Marrow Syndrome Manifest symptoms (occurs after about 3 weeks): Chills Fatigue (RBC) Infection (WBC) Hemorrhage (platelets) Prognosis: possible death in about one month from infection and hemorrhage

Bone Marrow Syndrome 100 – 300 cGy : bone marrow may recover 400 – 600cGy: few survivors 1000 cGy : no survivors LD50 for humans is taken as 250 - 300 cGy Survival can be improved with bone marrow transplants and modern medical care.

Radiation effects on the embryo and fetus Classic effects: Lethal effects induced by relatively small doses if before or immediately after implantation in the uterine wall Malformations when irradiated during organ formation Growth disturbances without malformation at all stages of fetal development

Embryo and fetus Miscellaneous effects on various body structures and functions. Main factors of importance are dose and stage of development

Fetal development Pre – implantation Major organogenesis Fetal stage Conception to day 10: all cells highly undifferentiated Major organogenesis Day 10 to 6 weeks : differentiation begins Fetal stage 6 weeks to birth

Pre - implantation Increased prenatal death Most sensitive stage to lethal effects If embryo survives, it grows normally in utero and afterwards. Few, if any, abnormalities are produced at this stage In mouse: 5 – 15 cGy can kill fertilized eggs

Major organogenesis Increased neonatal death Decreased prenatal death Principle effect is production of congenital structural abnormalities In mouse: 200cGyn can result in 100% abnormalities.

Major organogenesis Contrary to what is seen in animals, radiation induced malformations of body structures other than CNS are uncommon in humans Why is this so? Animal experiments are controlled and exact, but not with humans Human organogenesis is 1/15 gestation period. In mice it is 1/3. CNS org. takes longer time in humans

Major organogenesis CNS malformations: Microcephaly Hydrocephaly Micropthalmia Mental retardation

Fetal stage A variety of effects have been observed in animals: liver, kidney, bone marrow After fairly high doses: sterility, cancer High doses would be needed to kill the fetus at this period Permanent growth retardation

Experience in humans Medical exposures during the early part of the last century Survivors in Japan

generalizations Large doses (>250cGy) before 2-3 weeks, are not very likely to produce severe abnormalities but embryo deaths are likely. 4 – 11 weeks: severe abnormalities of many organs 11 – 16 weeks: Eye, skeletal, genital organ abnormalities

generalizations 16 – 20 weeks: some CNS abnormalities After 30 weeks gross structural abnormalities not likely, but there could be functional abnormalities. Hiroshima: 30/1600 mental retardations after exposure at 8 – 15 weeks. This is higher than normal.

summary Moderate doses of radiation can cause catastrophic effects on the developing embryo and fetus Effects depend on stage, dose and doserate Gestation is divided into: Preimplantation – 0 to 9 days Organogenesis – 10 days to 6 weeks Fetal stage – 6 weeks to term

summary Principle effects are: Growth retardation Embryonic, neonatal or fetal death Gross congenital malformation

summary LD50 is lowest during preimplantation Peak incidence of malformations occurs when fetus is irradiated during organogenesis Malformations other than CNS is uncommon in humans Data from Japan shows that microcephaly can result from air dose of 10 – 19 R

summary From medical x-ray exposure: low doses of in utero exposure can lead to an increase in cancer incidence in the first 10 – 15 years of life by a factor of 1.5 – 2 No comparable increase was seen in Japanese survivors MPD to fetus is 0.5 rem per gestation period