MEDRADSC 2X03 - Lecture 6 - Cell Survival Curves Cont.

what does the multi-target model assume about cells related to cell death?

they must sustain multiple hits to critical targets within it for cell death to occur

Is the extrapolation number (n) a real number? Why or why not?

No, because a cell cannot have survival greater than 100%

D0 is referred to as the mean ________ dose.

lethal

The expression, logen = Dq / D0 has an important limitation, what is it and what is not included in this expression used for the multi-target model?

It does not include D1, this is because the expression is not applied to the shoulder portion of the cell survival curve

what does the linear quadratic model assume about cell death?

there are two parallel components to cell killing, one proportional to dose and one proportional to square dose

what does the linear quadratic model recognize about cell killing?

chromosome damage may be due to a single radiation causing a DSB/mutation or two radiations causing two separate breaks

what is the surviving fraction equation?

S = e^(-aD - ßD^2)

what does D = a/ß mean

it means that the two components of cell killing make equal contribution to reduction of surviving fraction at a specific dose

in early responding tissues, what size of a/ß do we see?

large, about 10 Gy

what are examples of early responding tissues?

skin and mucosa

what are examples of late responding tissues?

lung and spinal cord

in late responding tissues, what size a/ß do we expect to see?

small, about 2 Gy

what is a limitation/problem with the theory of a/ß ratio?

in clinical settings, multiple organs and tissues are irradiated simultaneously, and not all of them respond the same

limitations to the linear quadratic survival curve

it is a continuously bending curve, it only fits experimental in vitro data for the first generations and the initial region of the curve correlates best with clinical data (linear portion)

what are the limitations of using in vitro cell survival curves?

the reproductive integrity is not the only clinically relevant endpoint, tumour cells have poor plating efficiency and is difficult to determine surviving fraction at 2Gy and each tumour type varies in radiosensitivity

bystander effect

induction of biological effects in un-irradiated tissues that neighbour irradiated tissues

what data supports the bystander effect?

narrow beam radiation to cell culture and then addition of irradiated cells to non-irradiated cells - both show cell killing

fractionation

the division of a dose of radiation into smaller doses prolonged over a period of time to allow for cell repair

compare a/ß ratios for normal tissues and cancerous tissues

a/ß is higher for tumours, and lower for regular tissues

what is considered a large a/ß ratio? what types of tissues does this occur in?

10, early responding tissues and mostly tumours

what is considered a small a/ß ratio? what types of tissues does this occur in?

2, late responding tissues, potentially prostate cancer