p53: biology and role for cellular radiosensitivity.

TY - JOUR

T1 - p53: biology and role for cellular radiosensitivity.

AU - Dahm-Daphi, Jochen

PY - 2000

Y1 - 2000

N2 - PURPOSE: p53 is the most commonly mutated gene in human tumors with large impact on cellular biology and response to radiation. Many excellent reviews are available on various aspects but for several years none about the role of p53 for radiosensitivity. The latter is the aim of the present paper. METHODS: Review of the literature. RESULTS: p53 is a regulator of apoptosis mainly in hematopoetic tissue. In normal tissue and solid tumors presumably other functions have more impact on the cellular response. p53 controls cell-cycle progression after irradiation and also DNA-repair, namely homologous and non-homologous recombination. Mutations of p53 alter these functions which may be responsible for an enhanced cellular and tumor radioresistance. At present only few reports were able to show that under tightly controlled conditions loss of p53 wild-type function leads to enhanced radioresistance. A general proof is still lacking. CONCLUSIONS: The emerging picture in the year 2000 shows p53 as a central protein in a multi-enzyme multi-function network which is far from being fully understood. Although p53 appears to be a major regulator it is certainly not the unreplaceable component the loss of which uniformly determines radioresistance. Only further understanding of modifiers and co-operators in the cell and in the specific tissue context will elucidate p53's role for radiosensitivity and radiotherapy.

AB - PURPOSE: p53 is the most commonly mutated gene in human tumors with large impact on cellular biology and response to radiation. Many excellent reviews are available on various aspects but for several years none about the role of p53 for radiosensitivity. The latter is the aim of the present paper. METHODS: Review of the literature. RESULTS: p53 is a regulator of apoptosis mainly in hematopoetic tissue. In normal tissue and solid tumors presumably other functions have more impact on the cellular response. p53 controls cell-cycle progression after irradiation and also DNA-repair, namely homologous and non-homologous recombination. Mutations of p53 alter these functions which may be responsible for an enhanced cellular and tumor radioresistance. At present only few reports were able to show that under tightly controlled conditions loss of p53 wild-type function leads to enhanced radioresistance. A general proof is still lacking. CONCLUSIONS: The emerging picture in the year 2000 shows p53 as a central protein in a multi-enzyme multi-function network which is far from being fully understood. Although p53 appears to be a major regulator it is certainly not the unreplaceable component the loss of which uniformly determines radioresistance. Only further understanding of modifiers and co-operators in the cell and in the specific tissue context will elucidate p53's role for radiosensitivity and radiotherapy.

M3 - SCORING: Zeitschriftenaufsatz

VL - 176

SP - 278

EP - 285

JO - STRAHLENTHER ONKOL

JF - STRAHLENTHER ONKOL

SN - 0179-7158

IS - 6

M1 - 6

ER -