Comparable radiation response of ex vivo and in vivo irradiated tumor samples determined by residual γH2AX.

PURPOSE

a) To investigate if an ex vivo cultured and irradiated tumor biopsy reflects and predicts the radiation response of the corresponding in vivo irradiated tumor measured with the DNA double strand break marker γH2AX foci.

MATERIALS AND METHODS

Five human head and neck squamous cell carcinoma (hHNSCC) xenograft models were used. Fine needle biopsies were taken from anesthetized tumor-bearing NMRI nude mice prior to in vivo single dose irradiation (0, 2, 4, or 8 Gy) under ambient blood flow. Biopsies were ex vivo reoxygenated and irradiated with equivalent doses. Tumors and biopsies were fixed 24 h post irradiation, and γH2AX foci were assessed in oxygenated tumor regions.

RESULTS

Linear regression analysis showed comparable slopes of the residual γH2AX foci dose-response curves in four out of five hHNSCC models when in vivo and ex vivo cohorts were compared. The slopes from ex vivo biopsies and in vivo tumors could classify the respective tumor model as sensitive or resistant according to the intrinsic radiation sensitivity (TCD).

CONCLUSION

The ability of ex vivo irradiated tumor biopsies to reflect and predict the intrinsic radiation response of in vivo tumors increases the translational potential of the ex vivo γH2AX foci assay as a diagnostic tool for clinical practice.