Analysis of chromosome aberrations by FISH and Giemsa assays in lymphocytes of cancer patients undergoing whole-body irradiation: comparison of in vivo and in vitro irradiation.
OBJECTIVE
To study the cytogenetic effects of fractionated radiotherapy in peripheral blood lymphocytes of five cancer patients. In vitro experiments were performed in parallel using the same dose range and a comparison was made of the induced frequencies of stable and unstable chromosome aberrations. The object was to clarify the use of an in vitro calibration curve for immediate and retrospective dosimetry in cases of radiation accidents.


METHODS
Patients were exposed to 60Co gamma-rays at a single dose of 11.5 cGy each day up to a total dose of 57.5 cGy, given in 5 days. For measurement of chromosome aberrations, blood was collected from patients before irradiation and after each exposure. Blood taken before treatment was used as a control and for in vitro irradiation experiments in the dose range 8-50 cGy. Chromosome aberration frequency (stable as well as unstable) was determined using fluorescence in situ hybridization (FISH) assay with specific DNA libraries for chromosomes 1, 4 and 8 and a pancentromertic probe for the whole genome. Giemsa-stained preparations were used to score unstable aberrations following in vivo and in vitro exposure.


RESULTS
A linear dose-response curve was determined for both dicentrics and translocations. The in vivo frequency of translocations was higher than for dicentrics. Dose-response curves generated for translocations following in vivo and in vitro irradiation yielded similar frequencies. In contrast, for dicentrics, in vitro irradiation yielded a higher frequency when compared with data generated following in vivo exposure.


CONCLUSIONS
For dose reconstruction purposes, translocations frequency seems to be a more adequate end-point than the scoring of dicentrics. The established in vitro calibration curve for dicentrics may underestimate absorbed radiation dose in cases of protracted exposure.
Vorobtsova
I
I
Laboratory of Radiation Genetics, Central Research Institute of Roentgenology and Radiology, Pesochny, Leningradskaya 70/4, 197758, St Petersburg, Russia. radgen@gate.la.spb.ru
Darroudi
F
F
Semyonov
A
A
Kanayeva
A
A
Timofeyeva
N
N
Yakovleva
T
T
Zharinov
G
G
Natarajan
A T
AT
D000328:Adult; D000368:Aged; D001399:Azure Stains; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D020732:Cytogenetic Analysis / Q000379:methods; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008214:Lymphocytes / Q000502:physiology* / Q000528:radiation effects*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics* / Q000532:radiotherapy*; D014916:Whole-Body Irradiation
D001399:Azure Stains