Factors Affecting Radiation Effect To Cell

RADIATION CELL DAMAGE

RADIATION SCIENCE

OBJECTIVES

• Understand definition of ionzing radiation
• Identify types radiation
• Highlight examples of ionizing radiation

Explain direct and indirect mechanism of cell damage Understand how physical, chemical and biological factors contribute to cell damage by radiation

INTRODUCTION

• What is ionizing radiation?
• Types of radiation
• Examples of ionizing radiation

Explain direct and indirect mechanism of cell damage by radiation

FACTORS WHICH MODIFY CELL DAMAGE BY RADIATION

• Physical factors
• Biological factors

Chemical factors

PHYSICAL FACTORS

• Linear energy transfer
• Relative biological effectiveness

Protraction and fractionation

PHYSICAL FACTORS

LINEAR ENERGY RANSFER

-Linear energy transfer (LET) is a measure of the rate at which energy is transferred from ionizing radiation to soft tissue -LET is expressed in units of kiloelectron volt of energy transferred per micrometer of track length in soft tissue (keV/µm).

-The ability of ionizing radiation to produce a biologic response increases as the LET of radiation increases. When LET is high, ionizations occur frequently, increasing the probability of interaction with the target molecule The LET of diagnostic x-rays is approximately 3 keV/µm

ii. Relative Biologic Effectiveness

• As the LET of radiation increases, the ability to produce biologic damage also increases.

This effect is quantitatively described by the relative biologic effectiveness (RBE)

Factors Affecting Radiation Effect To Cell

Diagnostic x-rays have an RBE of 1. Whereas radiations with lower LET than diagnostic x-rays have an RBE less than 1, radiations with higher LET have a higher RBE.

iii. Protraction and Fractionation

-If a dose of radiation is delivered over a long period of time rather than quickly, the effect of that dose is less.

-Stated differently, if the time of irradiation is lengthened, a higher dose is required to produce the same effect.

This lengthening of time can be accomplished in two ways. If the dose is delivered continuously but at a lower dose rate, it is said to be protracted. Six gray (600 rad) delivered in 3 -minutes at a dose of 2 Gyt/min is lethal for a mouse. However, when 6 Gyt is delivered at the rate of 10 mGyt/hr for a total time of 600 hours, the mouse will survive.

Factors Affecting Radiation Effect To Cell

If the 6-Gyt dose is delivered at the same dose rate, but in 12 equal fractions of 500 mGyt, all separated by 24 hours, the mouse will survive. In this situation, the dose is said to be fractionated.

Radiation dose fractionation reduces effect because cells undergo repair and recovery between doses. Dose fractionation is used routinely in radiation oncology.

BIOLOGIC FACTORS THAT AFFECT RADIOSENSITIVITY AND CELL DAMAGE

• Oxygen effect
• Age

Recovery

Oxygen Effect

-Tissue is more sensitive to radiation when irradiated in the oxygenated, or aerobic, state than when irradiated under anoxic (without oxygen) or hypoxic (low-oxygen) conditions.

-This characteristic of tissue radiation response is called the oxygen effect and is described numerically by the oxygen enhancement ratio (OER).

ii. Age

• -The age of a biologic structure affects its radiosensitivity.
• -The response of humans is characteristic of this age-related radiosensitivity

-Humans are most sensitive before birth.

-After birth, sensitivity decreases until maturity, at which time humans are most resistant to radiation effects.

In old age, humans again become somewhat more radiosensitive.

iii. Recovery

-Human cells can recover from radiation damage.

-If the radiation dose is not sufficient to kill the cell before its next division (interphase death), then given sufficient time, the cell will recover from the sublethal radiation damage it has sustained.

-Some types of cells have greater capacity than others for repair of sublethal damage.

-At the whole-body level, this recovery from radiation damage is assisted through repopulation by surviving cells

If a tissue or organ receives a sufficient radiation dose, it responds by shrinking.

This is called atrophy, and it occurs because some cells die and disintegrate and are carried away as waste products.

If a sufficient number of cells sustain only sublethal damage and survive, they may proliferate and repopulate the irradiated tissue or organ

CHEMICAL FACTORS

• Radiosensitizers
• Radioprotectors

Free radicals/other molecules (water molecules)

Radiosensitizers

-Agents that enhance the effect of radiation are called sensitizing agents. Examples include halogenated pyrimidines, methotrexate, actinomycin D, hydroxyurea, and vitamin K.

-The halogenated pyrimidines become incorporated into the DNA of the cell and amplify the effects of radiation on that molecule. All radiosensitizers have an effectiveness ratio of approximately 2, that is, if 90% of a cell culture is killed by 2 Gyt (200 rad), then in the presence of a sensitizing agent, only 1 Gyt (100 rad) is required for the same percentage of lethality

ii. Radioprotectors.

Radioprotective compounds include molecules that contain a sulfhydryl group (sulfur and hydrogen bound together), such as cysteine and cysteamine.

Hundreds of others have been tested and found effective by a factor of approximately 2. For example, if 6 Gyt (600 rad) is a lethal dose to a mouse, then in the presence of a radioprotective agent, 12 Gyt (1200 rad) would be required to produce lethality

iii. Other molecules/water molecules

-Water molecules act as a medium for radiation-induced free radical generation, amplying damage through indirect mechanism