Possible transient adaptive response to mitomycin C in peripheral lymphocytes from thyroid cancer patients after iodine-131 therapy.
Our study attempted to assess the possible induction and persistence of an adaptive response in lymphocytes of thyroidectomized thyroid cancer patients treated with 131I (2,590 MBq, corresponding to whole body doses in the range of 200-300 mGy), to a testing dose of mitomycin C (MMC) in vitro. The cytogenetic endpoint studied was the induction of micronuclei in cytokinesis-blocked peripheral blood lymphocytes, immediately before treatment and 1, 6 and 24 months after therapy. One month after therapy, induction of micronucleated cytokinesis-blocked lymphocytes ( per thousand ) by MMC was lower (34.6 +/- 7.7) than before therapy (52.1 +/- 5.0). In 7 of 11 patients this reduction was significant. However, at 6 months, induction of micronuclei was markedly higher (133.1 +/- 13.6). This significant increase was observed regardless of the decrease at 1 month. At 24 months, the frequency of micronucleated cells decreased (84.8 +/- 5.5), but remained higher than before treatment. The results obtained 1 month after therapy could reflect adaptation due to radiation, or a higher rate of early apoptosis or cell death, with bone marrow suppression, visible as a lower response in vitro towards MMC. At 6 months, recovery of the lymphocyte population may occur, and higher responses to MMC in vitro could reflect higher chromosomal instability in the previously irradiated stem cells with a concomitant disappearance of adaptation, whereas at 24 months the results show a tendency to return to pretherapy values.
Monteiro Gil
Octávia
O
Department of Genetics, Faculty of Medical Sciences, New University of Lisbon, Lisbon, Portugal.
Oliveira
Nuno Guerreiro
NG
Rodrigues
António Sebastião
AS
Laires
António
A
Ferreira
Teresa Cruz
TC
Limbert
Edward
E
Rueff
José
J
D000222:Adaptation, Physiological / Q000528:radiation effects*; D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008214:Lymphocytes / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D008875:Middle Aged; D016685:Mitomycin / Q000494:pharmacology*; D013964:Thyroid Neoplasms / Q000235:genetics / Q000532:radiotherapy*
D000903:Antibiotics, Antineoplastic; D007457:Iodine Radioisotopes; D016685:Mitomycin