title: Long-term in vivo effects of cisplatin on gamma-H2AX foci signaling in peripheral lymphocytes of tumor patients after irradiation.
abstract: OBJECTIVE
  This study determined the effects of cis-diamminedichloroplatinum(II) on radiation-induced foci formation of gamma-H2AX and Rad51 in lymphocytes.
  
  
  METHODS
  Twenty-eight cancer patients were irradiated for intrathoracic, pelvic, or head and neck tumors and received simultaneous cisplatin containing chemotherapy. The effect of cisplatin on radiation-induced gamma-H2AX and Rad51 foci as a response to ionizing radiation-induced DNA double-strand breaks was measured in lymphocytes after in vivo and in vitro radiochemotherapy. The role of DNA-dependent protein kinase and ataxia-telangiectasia mutated kinase in gamma-H2AX signaling, the consequences of altered gamma-H2AX foci formation on double-strand break end joining, was studied.
  
  
  RESULTS
  Cisplatin decreased the number of induced gamma-H2AX foci in lymphocytes after in vivo or in vitro irradiation by 34% +/- 6% at days 0 to 3 after cisplatin (P < 0.0001) and remained significant until day 6. The variation in this cisplatin effect from patient to patient was larger than the retest error within the same patient (P = 0.01). The cisplatin effect was not accompanied by an inhibition of end joining of double-strand break as analyzed using gel electrophoresis of DNA under neutral conditions. Cisplatin also decreased radiation induced Rad51 foci formation in lymphocytes after stimulation of proliferation with phytohemagglutinin by 47% +/- 6% (P < 0.0001).
  
  
  CONCLUSIONS
  Cisplatin has long-term effects on the early double-strand break response of gamma-H2AX and Rad51 foci formation after ionizing radiation. Inhibition of sensing and processing of double-strand break by gamma-H2AX and Rad51 foci formation are important mechanisms by which cisplatin can alter the radiation response.
authors.affiliation: Department of Radiotherapy, University Hospital Essen, Essen, Germany.
authors.forename: Ali
authors.initials: A
authors.lastname: Sak
authors.forename: Sara
authors.initials: S
authors.lastname: Grehl
authors.forename: Marianne
authors.initials: M
authors.lastname: Engelhard
authors.forename: Arne
authors.initials: A
authors.lastname: Wierlemann
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Kaelberlah
authors.forename: Patricia
authors.initials: P
authors.lastname: Erichsen
authors.forename: Christoph
authors.initials: C
authors.lastname: Pöttgen
authors.forename: Michael
authors.initials: M
authors.lastname: Groneberg
authors.forename: Martin
authors.initials: M
authors.lastname: Stuschke