Characterization of Accelerated Iron-Ion-Induced Damage in Gap Junction-Competent and -Incompetent Thyroid Follicular Cells

Abstract

Early- and late-passage cultures of Fischer rat thyroid cells differ in their growth properties and gap junction competency. Previous studies comparing early- and late-passage cultures exposed to gamma rays and proton beams revealed that differences in growth rate did not influence their responses; however, the presence of connexin 32 gap junctions conferred resistance to gamma radiation. To further assess differences in radiation quality, suspension cultures of early- and late-passage cells were exposed to accelerated iron ions, and their comparative biological responses were measured. The iron-ion-irradiated cells displayed sustained levels of incorporated dUTP, reflecting persistent DNA damage. These results were supported by the frequency of chromosomal damage measured by micronucleus formation. Iron-ion irradiation induced micronuclei at a rate of eight per gray per 100 binucleated cells scored in early-passage cells and nine per gray per 100 binucleated cells scored in late-passage cells. Relative to photons, the calculated radiobiological effectiveness for frequency of micronuclei was 5.7 and 6.4 for the early- and late-passage cultures, respectively (P > 0.05). Levels of apoptosis fluctuated as a function of dose, and modest increases above basal levels persisted throughout the 48-h period. The comparison of retained follicular structures revealed differences in the alpha components of the linear-quadratic dose-response curves (0.60 Gy(-1) for early-passage and 0.71 Gy(-1) for late-passage cultures, P < 0.014). Cell cycle phase redistribution resulted in a G2 arrest (P < 0.001) for both early- and late-passage cultures. In conclusion, the response of thyroid follicular cells to high-LET radiation was not influenced by the presence of gap junctions or the proliferative status of the target cells.

Identification of a novel switch in the dominant forms of cell adhesion-mediated drug resistance in glioblastoma cells

“…The role of gap junctions in apoptosis signaling is a complex one, as both, cell-death and cell-survival signals, can spread between cells via this route (Krysko et al, 2005). Although gap junction-mediated apoptosis resistance has been described in other cell systems (Green et al, 2005), this study is, to our knowledge, the first to address this phenomenon in GBM cells.…”

The use of micronucleus test for detection of genotoxic damage to the thyroid gland

“…can induce pathological changes in TG, which is accompanied by stimulation of division and damage to the genome in glandular cells [4,10]. Micronucleus formation in cultured thyrocytes under the influence of radiation illustrates the necessity to perform detailed investigations of this problem [8,9].…”

Ploidy of micronucleated thyrocytes induced by methylnitrosourea injection

“…This is true primarily for highly specialized populations with low rejuvenation level, capable of retaining aberrant cells for a long time. For the population of follicular thyrocytes studies as a prospective test system for bioindication of genotoxic injuries to the thyroid gland (TG) [5,10] the question about ploidy of damaged cells remains not studied.…”