Jl. Schwartz et al., Evidence for the expression of radiation-induced potentially lethal damagebeing a p53-dependent process, INT J RAD B, 76(8), 2000, pp. 1037-1043
Purpose: To test the hypothesis that the expression of potentially lethal d
amage (PLD) is a p53-dependent process.
Materials and methods: Previously reported data on radiation sensitivity, D
NA double-strand break rejoining, PLD expression and repair (PLDR) were ana
lyzed for a group of 12 human tumor cell lines and three human diploid fibr
oblast cell lines. Seven of these cell lines had normal p53 gene expression
while the other eight were functionally p53-deficient. None of the cell li
nes was sensitive to radiation-induced apoptosis.
Results: Cell lines with a normal P53 expression were more sensitive to rad
iation, but only when sensitivity was measured in plateau-phase cultures un
der conditions where PLDR was minimized. Mutation or functional inactivatio
n of p53 by HPV E6-transformation led to a more radioresistant phenotype un
der these conditions as well as a significant reduction in PLDR. PLDR was i
nversely proportional to the percentage of radiation-induced DNA double-str
and breaks rejoined in Ih in the p53 normal cell lines.
Conclusions: These results suggest that the expression of PLD is primarily
a p53-dependent process. In the absence of functional p53 gene expression,
the effects of PLD are minimized. These observations help clarify the role
of p53 in tumor response to radiation therapy because they suggest that the
effects of alterations in p53 are highly dependent on the microenvironment
of the tumor, i.e. whether conditions allow for PLDR.