title: Micronuclei in lymphocytes of prostate cancer patients undergoing radiation therapy.
abstract: To further verify the applicability of the micronucleus (MN) assay in biodosimetry, we measured the MN yield in cytokinesis-blocked (CB) peripheral blood lymphocytes (PBL) of eight prostate cancer (PC) patients. These patients had no previous chemotherapy or radiotherapy (xRT). They were treated with standardized schemes of fractionated pelvic xRT. Before xRT, and at one random time-point during the course of xRT, blood samples were collected from each patient for the following purposes: (1) to verify the relationship between the MN yield in PBL and the estimated equivalent (EQ) total-body absorbed dose; and (2) to evaluate the individual differences of ex vivo radiation dose-response (1-4 Gy) relationship of MN yield in PBL before xRT. The number of xRT fractions, cumulative tumor dose, and EQ total-body absorbed doses of these patients represented a wide range. We found in PBL of these patients that (1) MN yield (Y) increased linearly with the estimated EQ total-body absorbed dose as Y=14.6+9.2D (R(2)=0.7, p=0.007); the distributions of MN yield were overdispersed; the ratio of relative increment of MN yield per 1000 binucleated (BN) PBL ranged from 0.9 to 8.2 (median: 4.1) folds above that of the respective baseline levels; and (2) before xRT, the MN yields also increased linearly with the ex vivo radiation dose; at each radiation dose level, the distributions of MN yield were overdispersed in most patients. In two of the three patients with xRT-induced early side effects (cystitis, diarrhea), the MN yield in PBL induced by ex vivo irradiation before xRT was significantly higher than in the other patients without xRT-induced side effects. These findings suggest that MN yields in CB PBL can be used as an in vivo biodosimeter. Since the differences in individual ex vivo radiation dose-response relationship of MN yield in PBL before xRT appeared to be significant, our preliminary results also suggest that it may be possible to identify individual intrinsic radiosensitivity before the start of xRT.
authors.affiliation: Department of Radiation Oncology, Leo W. Jenkins Cancer Center, Brody School of Medicine at East Carolina University, 275858, Greenville, NC, USA. leet@mail.ecu.edu
authors.forename: T K
authors.initials: TK
authors.lastname: Lee
authors.forename: K F
authors.initials: KF
authors.lastname: O'Brien
authors.forename: J L
authors.initials: JL
authors.lastname: Naves
authors.forename: K I
authors.initials: KI
authors.lastname: Christie
authors.forename: H H
authors.initials: HH
authors.lastname: Arastu
authors.forename: G S
authors.initials: GS
authors.lastname: Eaves
authors.forename: A L
authors.initials: AL
authors.lastname: Wiley
authors.forename: U L
authors.initials: UL
authors.lastname: Karlsson
authors.forename: M R
authors.initials: MR
authors.lastname: Salehpour
mesh_terms: D000368:Aged; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D006801:Humans; D008214:Lymphocytes / Q000473:pathology / Q000528:radiation effects*; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000528:radiation effects*; D015162:Micronucleus Tests; D011471:Prostatic Neoplasms / Q000097:blood / Q000532:radiotherapy*; D011879:Radiotherapy Dosage