Radiation-induced Gadd45 expression correlates with clinical response to radiotherapy of cervical carcinoma

Background: Recent work has identified a category of genes devoted to the c ontrol of genomic stability and prevention of cellular evolution, They enco de components of cell cycle checkpoint, i.e., regulatory pathways committed to ordered cell cycle transition and fidelity of replicated DNA under adve rse environmental conditions, such as those following exposure to genotoxic agents. Gadd45 belongs to the class II family of DNA damage-inducible (DDI ) gene, and its role in DNA repair has been proved in many experimental mod els. The aim of our study was to correlate gadd45 radio-induction with the responsiveness to radiotherapy of cervical carcinomas, a type of cancer mos t commonly treated with radiotherapy alone. Methods: By means of a competitive polymerase chain reaction strategy, we c ompared in 14 patients the gene expression levels before and during externa l beam radiotherapy, when a dose ranging from 18 to 25 Gy was delivered to the target. Results: We found a correlation between the lack of gadd45 induction and a good clinical response to radiotherapy, in terms of both local control and disease-free survival. Conclusion: Our results support the measure of the induction of gadd45, and possibly of other genes required for regulated G(1)-S checkpoint, as a met hod useful for prognostic evaluation of cervical carcinoma patients. (C) 20 00 Elsevier Science Inc.