Construction and validation of joint dose-response curves for chromosome aberrations and interphase lymphocyte survival for cytogenetic biodosimetry of partial exposure.

PURPOSE: Cytogenetic biodosimetry of the Partial Body Irradiation (PBI) requires a dose response curve (DRC) for chromosome aberrations (ChA) but also an exponential coefficient D0 of the interphase cell survival (ICS) of irradiated lymphocytes. The aim of the present work was to construct joint DRCs in vitro for ChA and ICS and validate them in a setting with a limited number of blood donors.

MATERIALS &

METHODS

Blood samples from three healthy volunteers were irradiated in vitro with 6 MV Linac photons to a range of acute doses up to 5.46 Gy. Cytogenetic preparations were stained with Fluorescence-plus-Giemsa; ChA were scored in the first division metaphases. The ICS was assessed in PBI simulations, mixing irradiated and unirradiated blood 1:1 at each dose point; D0 was estimated by regression analysis.

RESULTS

The DRC for dicentrics had linear and quadratic coefficients, respectively, 0.031 × cell-1 × Gy-1 and 0.070 × cell-1 × Gy-2; for dicentrics plus centric rings - respectively, 0.033 × cell-1 × Gy-1 and 0.083 × cell-1 × Gy-2. The ICS parameter D0 varied within 3.18 - 3.54 Gy, depending on the end-point used for the assessment. DRCs were successfully validated in a biodosimetry exercise with uniform irradiation and PBI simulations in vitro and using in vivo data from four breast cancer patients after their first radiotherapy dose fraction.

CONCLUSIONS

Generating joint DRCs for ChA and ICS in a single experiment can be recommended as a rational methodology for laboratories practicing cytogenetic biodosimetry.