Evidence for predictive validity of blood assays to evaluate individual radiosensitivity.
OBJECTIVE
An escalation in standard irradiation dose ensuring improved local tumor control is estimated, but this strategy would require the exclusion of the most sensitive individuals from treatment. Therefore, fast and reliable assays for prediction of the individual radiosensitivity are urgently required.


METHODS
Seven parameters in lymphocytes of 40 patients with leukemia were analyzed before, during, and after total body irradiation (TBI) and in vitro X-ray irradiation. These were: cell proliferation, nuclear damage, activation of cytokines, and numbers of total leukocytes of CD34+ hematopoietic blood stem cells and of CD4+ and CD8+ lymphocytes. Additionally, antioxidative capacity of blood plasma, uric acid, and hemoglobin levels were measured. Blood samples of 67 healthy donors were used as controls.


RESULTS
In vivo and in vitro irradiations showed comparable results. A dose-response relationship was found for most parameters. Three parameters were associated with severe acute oral mucositis (Grade 3 or 4 vs. Grade 0 to 2): leukocytes fewer than 6200/microL after 4 Gy TBI, a rate of >19% lymphocytes with reduced DNA and protein content ("necroses") after 4 Gy in vitro irradiation, and a small antioxidative capacity in blood plasma (<0.68 mMol) after 8 Gy TBI.


CONCLUSIONS
Three simple blood assays were associated with oral mucositis that are posed here hypothetically as an early symptom of enhanced radiosensitivity in leukemic patients: leukocyte count, damaged lymphocyte score, and the antioxidative capacity after exposure.
Severin
Erhard
E
Institute of Radiation Biology, University Hospital, Münster, Germany. severie@uni-muenster.de
Greve
Burkhard
B
Pascher
Elke
E
Wedemeyer
Niels
N
Hacker-Klom
Ursula
U
Silling
Gerda
G
Kienast
Joachim
J
Willich
Normann
N
Göhde
Wolfgang
W
D000293:Adolescent; D000328:Adult; D002453:Cell Cycle / Q000528:radiation effects; D016207:Cytokines / Q000097:blood; D004307:Dose-Response Relationship, Radiation; D005240:Feasibility Studies; D005260:Female; D006412:Hematopoietic Stem Cells / Q000528:radiation effects; D006801:Humans; D007938:Leukemia / Q000097:blood* / Q000532:radiotherapy*; D007958:Leukocyte Count; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000473:pathology / Q000528:radiation effects*; D008223:Lymphoma / Q000097:blood / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000528:radiation effects; D052016:Mucositis / Q000097:blood / Q000209:etiology*; D011446:Prospective Studies; D011836:Radiation Tolerance / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012737:Sex Factors; D014527:Uric Acid / Q000097:blood; D014916:Whole-Body Irradiation
D016207:Cytokines; D017382:Reactive Oxygen Species; D014527:Uric Acid