Radiation morbidity and micronuclei in lymphocytes of prostate cancer patients

Abstract

15540 Background: Since formation of micronuclei (MN) in interphase cells is a reflection of DNA damage, it has been postulated that enhanced peripheral blood lymphocytes (PBL) radiosensitivity might correlate with the development of radiation morbidity. Methods: We conducted the cytokinesis-block (CB) MN assay of PBL in 54 prostate cancer (PC) patients ( mean age ± SEM: 68 ± 1.6 yrs) who had no previous exposure to cytotoxic agents. Patients received standardized pelvic radiotherapy (RT) (41.4 -50.4 Gy) with mean follow-up of 29.1± 3.3 mos. Blood samples were drawn before RT and at designated intervals after RT initiation. Gastrointestinal (GI) and genitourinary (GU) morbidity were determined using RTOG criteria. Results: Average reactors (AR, n = 14) were defined as patients who did not develop morbidity. Grade 1 (G1R, n = 19) and Grade 2 reactors (G2R, n = 21) were defined as those who developed Grade 1 or Grade 2 GI or GU morbidity, respectively. Results of the MN yield in PBL before RT indicated that (1) at baseline level (0 Gy), differences in MN yield for AR, G1R, and G2R patients were insignificant; (2) after ex vivo irradiation (1 - 4 Gy), MN yield followed a linear-quadratic polynomial trend in AR, G1R, and G2R patients; and (3) differences in MN yield in AR vs. G1R or AR vs. G2R patients were significant (P = 0.0001). After the initiation of RT, MN yields in PBL at 24 h, one week, and six weeks, the ratio of relative increment (RI) of RT-induced MN yield, i.e. MNRI = MN (RT-induced) - MN (pre-RT)/ MN (pre-RT) in both G1R and G2R patients was significantly higher than that in AR patients. Our results suggest that prediction of GI or GU morbidity in patients is potentially possible through the evaluation of both ex vivo radiation dose-response relationship of MN in PBL before the initiation of RT and the in vivo MNRI after RT. No significant financial relationships to disclose.