P53 INDUCTION AS A PREDICTOR OF RADIATION COMPLICATIONS

Project: Research project

Project Details

Description

The ability to predict the response of normal tissues to a given course of
radiation might allow a clinician to anticipate and avoid undue toxicity.
Recent studies have demonstrated that the intrinsic radiosensitivity of
skin fibroblasts from individual patients is predictive of the severity of
acute and late radiation reactions experienced by these patients. While
radiosensitivity assays are cumbersome, newer techniques which measure DNA
double strand breaks (dsb) or the level of p53 induction (a central
molecule involved in radiation-induced apoptosis) following irradiation may
prove to be useful as predictive assays.

The primary goal of this project will be to assess whether these assays
performed on skin fibroblasts obtained form patients treated with radiation
are predictive for acute or late skin reactions. Early passage fibroblast
cell lines will be established from 26 breast cancer patients exhibiting
severe skin reactions and from case-matched controls treated on a
prospective radiation fractionation trial at the Royal Marsden Hospital.
DNA dsb will be measured with pulse-field gel electrophoresis or single-
cell gel electrophoresis. The levels of p53 and WAF1 (a downstream
effector of p53) induction will be measured by various methods including
Western blotting, enzyme linked immunosorbent assay, electrophoretic
mobility shift assay and Northern blotting.

We hypothesize that the level of DNA dsb induction following in vitro
irradiation of skin fibroblasts should correlate with p53 induction, and
that higher levels of p53 and DNA dsb induciton may predict for more severe
acute or late normal tissue reactions in patients. The ability to
accurately predict the severity of radiation reactions can potentially aid
the clinician in planning a course of radiotherapy.
StatusNot started

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