chapter 7: Molecular and cellular radiation biology

ionizing radiation

damages living systems by ionizing the atoms comprising the molecular structure of these systems

linear energy transfer (LET)

the average energy deposited per unit length of track by ionizing radiation as it passes through and interacts with a medium along its path

very important factor in assessing potential tissue and organ damage from exposure to ionizing radiation

low let radiation

gamma rays

x-rays

high let radiation

alpha particles

ions of heavy nuclei

charged particles released from interactions between neutrons and atoms

low energy neutrons

as LET increases

the quality factor for a given form of radiation will increase

high relative biologic effectiveness (RBE)

high LET

oxygen enhancement ratio (OER)

the ratio of the radiation dose required to cause a particular biologic response of cells or organisms in any oxygen- deprived environment to the radiation dose required to cause an identical response under normal oxygenated conditions

more oxygen in cell

more radiosensitive

more hypoxic

more damage can be done

more RBE

molecular

cellular

organic systems

biologic damage stemming from exposure to ionizing radiation may be observed on three levels

disrupted

if a sufficient quantity of somatic cells are affected, entire body process may be ____

direct action

found in DNA

indirect action

found in water

indirect

because the human body is 80% water and less than 1% DNA, essentially all effects of low- LET irradiation in a living cell result from ___ action

radiolysis of water

ionization of water molecules

production of free radicals-highly reactive and unstable substance

single-strand break

ionizing radiation interacts with DNA macromolecule, transfers energy, and ruptures one of the molecule’s chemical bonds possibly severing one of the sugar phosphate chain side rails (point mutation)

repair enzymes are often capable of reversing this damage

double-strand break

further exposure of the affected DNA macromolecule to ionizing radiation can lead to additional breaks in the sugar-phosphate molecular chain(s)

breaks can be repaired but not as easily as single-strand breaks

if repairs does not take place further separation may occur in the DNA chains, threatening the life of the cell

commonly in high LET/ densely ionizing

Rung of DNA

result is a cleaved or broken chromosome with each new portion containing an unequal amount of genetic material

if broken chromosome divides, each new daughter cell will receive an incorrect amount of genetic material culminating in the death or impaired functioning of the new daughter cell

mutation

interactions of ionizing radiation with DNA molecules may cause the loss of or change in a nitrogenous base in the DNA chain

may not be reversible and may cause acute consequences for the cell

if cell remains viable, incorrect genetic information will be transferred to one of the two daughter cells when the cell divides

covalent cross-links

chemical unions created between atoms by the single sharing of one or more pairs of electrons

initiated by high-energy radiation

restitution

chromatid :whereby the breaks rejoin in the original configuration with no visible damage

deletion

part of the chromosome is lost at the next cell division, thus creating an acentric fragment

target theory: Master, or key, molecule

maintains normal cell function is believed to be present in every cell

necessary for the survival of the cell

used to explain cell death and nonfatal cell abnormalities caused by exposure to radiation

effects of irradiation on the entire cell

instant death

reproductive death

apoptosis, or programmed cell death

mitotic of genetic death

miotic delay

interference with function

more cell sensitivity

more cell damage

survival curves for mammalian cells

cell survival curve is a classic method of displaying the sensitivity of a particular type of cell to radiation

cell radiosensitivity

cell maturity and specialization (less radiosensitivity)

law of Bergoine and Tribondeau

established that radiosensitivity was a function of the metabolic state of the cell receiving the exposure

states the radiosensitivity of cells is directly proportional to their reproductive activity and inversely propotional to their degree of differentiation

more reproductive= more sensitive

less differentiation= less radiosensitive

erythrocytes

less radiosensitive

whole- body doses in excess

5 Gyt

lymphocytes

most radiosensitive blood cells

aberrations in lymphocytes from high level fluoroscopy

epithelial tissue

highly radiosensitive tissue

muscle tissue

highly specialized and do not divide

insensitive

nerve tissue in human adult

highly specialized and do not divide

insensitive

nerve tissue in embryo-fetus

more radiosensitive

max sensitivity 8-15 weeks

after week 25 risk is the same as young adult

2 Gyt

cause temporary sterility

5-6 Gyt

permanent sterility

0.1 Gyt

may cause genetic mutations

ova

immature are very radiosensitive

mature has less radiosensitivity

ovaries

of the female fetus and young child are very radiosensitive

women 20-30

are lowest level of radiosensitivity