RADIOBIOLOGY AND RP CD # 4 GENETIC EFFECTS REVISED OCT 2006 PG1 #1 Geneitc effects of radiation and DNA - all radiation damage starts with a single photon – different chains of events can occur Usually results in insignficant damage to a water molecule or cell Ocassionally biologic damage that results in genetic effects can occur #9 When DNA is damage – can result in cell death. One cell is not a problem – that many cells affected in a small area - when this happens , tissue or organs can be damaged or distroyed. # 10 The importance of DNA as a storehouse of genetic information – Each cell has a nucleus where DNA with other molecules form chromosomes. The chormosomes control growthand development of cells and orgarns – affecting ghe characteristics of a person. Changes in the genetic code can alter the cell’s growth and function Dna – Chromosome – Cell – Tissue – Organs – Human 16 – CELL DIFFERIATION – ALL CELLS CONTAIN GENES – WHICH GENES ARE TURNED ON DETERMINES WHAT TYPE OF CELL IT WILL DEVELOP INTO Why are there defferent kinds of cells? What causes a cell to develop into a muscle or bone cell? The function is determined by which genes are TURNED ON in each cell (the same instruction book – but different pages) 17 – GENES STORED IN CHROMOSOMES Humans have 46 chromosomes in 23 pairs –each pair has a maternal and parternal chromosome - when they combind in a daughter cell – there are over 16 million possible combinations 19 – Each person inherits half of their genes from mother and father. Dominant will be expressed over recessive GENERAL PRINCIPLES OF GENETIC INHERITANCE DOMINANT gene + DOMINANT gene = DOMINANT EXPRESSION DOMINANT gene + RECESSIVE gene = DOMINANT EXPRESSION RECESSIVE gene + RECESSIVE gene = RECESSIVE EXPRESSION (but not all genes are completely dominant – so sometime the recessive can sneak through) Example eye color: Blue eyes recessive Brown eyes - dominant 20 - Sex Linked Genes – RADIOBIOLOGY AND RP CD # 4 GENETIC EFFECTS REVISED OCT 2006 PG2 Males have only one X chromosome – so some mutations can expressed without having the complementary gene – these will appear in the first generation of males - Common sex linked gene is color blindness and hemophilia Since females have 2 X – they always require a matching – so females can pass on the disorder without expressing it. 24 – Common Gene Mutations 25 – MOST RADIATION-INDUCED GENETIC MUTATIONS ARE RECESSSIVE – THEREFORE ARE NOT EXPRESSED (SEEN) FOR GENERATIONS Radiation is thought primarily to cause recessive mutations – so if any form of genetic mutation does occur due to low doses of radiation. the chance of actually expressing it is very low Both parents must have the mutated recessive gene to pass it on 32- Chromosome have been damaged – when recombined they are missing significant genetic material – that will eventually cause cell death 42 – RISK ESTIMATES – based on probabilities of large populations MALE MORE LIKELY THAN FEMALE TO TRANSMIT GENETIC MUTATION– SOON AFTER RADIAITON (SPERM LIFE) HIGHEST RISK – MALE SPERM THAT FERTILIZE OVUM WITHIN SEVERAL MONTHS OF IRRADIATION Reduce the risk of passing on mutations by postponing conception of a child until the risk is minimized 43 LIFE SPAN SHORTENING CHART Radiography is a safe occuapation! RISK RISK OF DECREASING LIFE SPAN EXPECTED DAYS LOST Being MALE Heart Disease Smoking (1pk/day) Accidents Occupational Accidents Radiation Workers 2800 2100 1600 (4.3 years) 435 74 12 ( 1 day per Rad ?) RADIOBIOLOGY AND RP CD # 4 GENETIC EFFECTS REVISED OCT 2006 PG3 46 conclusions 1. Different mutations have different radiosensitivities 2. Same dose given over a longer period of time = less mutations 3. Males are more sensitive to radiation than females 4. Germ cells (sperm & ovum)are at risk at all doses of radiation 5. Most radiation induced mutations are recessive 6. Radiation induced mutations are very rare 47 NO SIGNIFICANT GENETIC MUTATIONS SEEN WITH A BOMB SURVIVORS Although studies indicate a clear connection between radiation and genetic mutations. Therefore is was assumed that children born to A-bomb survivors in Japan would also show genetic mutations. In Fact – this has not been the case. Studies of 3 generations of survivors have not shown any increase in genetic mutations – when these children were compared to other Japanese children. The lack of genetic mutations resulting form the Atomic bomb does not mean that genetic mutations did not occur – there were some trends to indicate a possible increase in certain genetic mutations. Radiation-induced genetic mutations are unique and are extremely rare. # 48 MALES MORE SENSITIVE THAN THE FEMALES MORE EXTERNAL GONADS – MORE LIKELY TO ABSORB RADIATION In males, sperm is continually being reproduced from stem cells – this stage is the most radiosensitive and any damage at this time can be passed along to the sperm that develop In Females – the follicle is the most radiosensitive stage, but there is also more time for repair before producing ova # 49 25 – 50 RAD DOSE CAN CAUSE GENETIC MUTATIONS Advisable to wait several months to conceive if dose is above 10 rad for female Males are advised to wait several month to procreate– GET RID OF DAMAGED SPERM APPROXIMATE DOSE: BE = 8 RAD FOR FEMALES HIP = 3.7 RAD FOR MALES