Comparisons of dose-response parameters for radiation-induced acentric fragments and micronuclei observed in cytokinesis-arrested lymphocytes

Abstract

We employed cytochalasin B to block cytokinesis in human lymphocytes exposed to 220 kV X-radiation. When 3 micrograms/ml of cytochalasin B was used, most cells escaped the block whereas at 6 micrograms/ml greater than 90% of the mitogen-responsive cells became binucleate. Using the higher concentration of cytochalasin B, we observed a linear-quadratic (i.e. Y = gamma + alpha D + beta D2) dose dependency for X-ray-induced micronuclei (MN) in preparations from three donors. When dose-response parameters were compared with those for total acentrics scored in first division metaphases, we observed no significant differences in estimates of the background (gamma) or linear (alpha) coefficients, but a 2-fold reduction in the beta coefficient for MN. We interpret our data as providing evidence that radiation-induced micronuclei are derived from acentric fragments (AF); that virtually all AF are recovered as MN in binucleate interphase daughter cells at low radiation doses; and that for our data, the relative proportion of AF that will be observed as independent MN decreases by a constant factor of approximately one-half as radiation dose increases.

DNA damage-related gene expression as biomarkers to assess cellular response after gamma irradiation of a human lymphoblastoid cell line

“…Moreover, radiosensitivity has frequently been asssessed by measuring DNA double-strand breaks using electrophoretic (Foray et al, 1997), cytogenetic (Little®eld et al, 1989) techniques, or cytokinesis-block micronucleus assay (Fenech, 1997). Therefore, it is essential to develop molecular multiparametric approaches in order to improve knowledge of cellular pathways involved in response to radiation, since such biomarkers could be critical for the follow-up of cancer patients treated by radiotherapy, or of healthy people accidentally exposed to radiation.…”

Change in centromeric and acentromeric micronucleus frequencies in human populations after chronic radiation exposure

“…Many fewer kinetochore-containing MN were identified after X-irradiation of human melanoma cells (Weissenborn and Streffer, 1991) or γ-irradiation of human lymphocytes (Littlefield et al, 1989) or fibroblasts (Cornforth and Goodwin, 1991). However, the rate of exposure was associated with the probability of acentric fragments being included in the MN.…”

“…However, the rate of exposure was associated with the probability of acentric fragments being included in the MN. With acute high doses of radiation exposure, acentric fragments would be less likely to be incorporated into single MN separately and there would be a tendency to form MN with multiple acentric fragments (Littlefield et al, 1989). If this could be applied to low dose rate exposure of the subjects in this study, acentric fragments could be fully expressed as independent MN.…”

Flow‐cytometric enumeration of micronucleated polychromatic erythrocytes in mouse peripheral blood

“…However, at doses above 0.1 Gy there was no significant further increase of the mean DNA content (data not shown). Littlefield et al (12) observed a dose-dependent increase of the proportion of large micronuclei in human lymphocytes irradiated in vitro with X-rays. They took this observation as an indication that at higher doses multiple acentric chromosome fragments are enclosed in a single micronuclear membrane.…”