Apoptosis, p53 and DNA damage in human lymphoblast cells : relation to cell death after radiation

الملخص EN

Purpose : to analyse the importance of both clonogen-ic and apoptotic death of lymphoblast cells after ionising radiation and their relation to p53 expression and radiosen-sitivity.

Materials and methods : Two lymphoblastoid cell lines differing in the expression of p53 (p53wt and p53mut) were compared as regards (a) intrinsic radiosensitivity by clonogenic assay, (b) initial and residual DNA double strand breaks (DSBs) as determined by constant field gel electrophoresis, and (c) induction of apoptosis as assayed by agarose gel electrophoresis.

Results : as expected the p53wt cell line was 4-fold more radiosensitive than the p53mut line as measured by the surviving fraction after 2 Gy (SF2).

The initial DSB induction did not differ in the two lines.

The fast repair component during the first post-radiation hour did not differ in the two lines.

This was followed by a slow repair component which appeared earlier in the p53wt cell line as indicated by the values at two hours.

The 2h-interval was chosen due to a renewed increase in the fraction of DNA release that coincided with induction of apoptosis.

As expected apoptosis appeared earlier in p53wt line and was greater in magnitude.

Conclusion : these results support the concept that intrinsic radio sensitivity in p53wt line is not related to induction of DSBs but apparently correlates with the slow repair component and the magnitude of the apoptotic response.