M.M. Elkind

Fission-spectrum neutrons at a low dose rate enhance neoplastic transformation in the linear, low dose region (0-10 cGy)

The neoplastic transformation of C3H 10T1/2 cells induced by fission-spectrum neutrons delivered at a high dose rate is linear up to 40 cGy. Reducing the dose rate increases the frequency of transformation in the low dose region. At a dose rate of 0.086 cGy min-1, the initial part of the induction curve remains linear but it has a slope 9-fold greater than the initial part of the curve at a high dose rate.

Two forms of potentially lethal damage have similar repair kinetics in plateau- and in log-phase cells

The effect on the survival of X-irradiated Chinese hamster cells (line V79) of two different post-treatments is examined in plateau- and in log-phases of growth. Qualitatively similar results are obtained with cells in both growth phases; that is, similar reductions in survival are effected by post-treatments with hypertonic phosphate buffered saline, and similar increases in survival are effected by post-treatments with conditioned medium. In addition, in both kinds of cells the kinetics of the repair processes are similar even though the kinetics of the two processes differ from each other considerably. While the results indicate that there can be essential differences in the type and/or the pathways of repair of potentially lethal damage, they also illustrate a broader meaning of this term than has been customary. Considered relative to the amount of DNA damage that can be expected to be potentially lethal, it is concluded that the two types of damage that are the subjects of this study represent only small sectors of the total amount of potentially lethal damage.

Enhanced Sensitivity to Neoplastic Transformation by 137Cs γ-rays of Cells in the G2-/M-phase Age Interval

C3H mouse 10T1/2 cells, exposed to low doses of fission-spectrum neutrons, have an enhanced frequency of neoplastic transformation if protracted exposures are used (Hill et al. 1982, 1984a, 1985). To explain this anomaly, a biophysical model was proposed (Elkind 1991a,b) having the following essential features: (1) a narrow age interval exists in the growth cycle of 10T1/2 cells in which cells have high sensitivities to transformation; (2) in the latter age interval, cells are also sensitive to killing; (3) with increasing dose, cells at ages earlier in the growth cycle are progressively delayed from entering the sensitive age window; and (4) with increasing dose, the transformation sensitivity of cells in the sensitive window is not expressed due to increased killing. Protracted low doses result in elevated frequencies because of less killing, and reductions in delays in cell progression. Therefore, transformation-sensitive cells can progress into the sensitive interval to replace those that have progressed out of it. The unique shape and radiobiological properties of cells in and around mitosis, led to the proposal that the sensitive window is mitosis and possible cells just preceding or just following M phase (Elkind 1991a,b). Because of the likelihood that the properties of the cells in a sensitive window would not be evident only when fission-spectrum neutrons are used, this study was undertaken using 137Cs gamma-rays. We have found that late G2- to M-phase 10T1/2 cells have a maximal sensitivity to neoplastic transformation as well as to killing by 137Cs gamma-rays.

Caffeine and D2O Medium Interact in Affecting the Expression of Radiation-induced Potentially Lethal Damage

Earlier work (Ben-Hur et al. 1980) has been extended to compare the killing of log-phase V79 Chinese hamster cells by ionizing radiation when they are treated immediately after irradiation with medium containing either caffeine or 90% D2O. The object was to determine if the enhanced killing due to post-treatment with caffeine, or D2O, resulted from action on the same sector of potentially lethal damage as appeared to be the case for hypertonic shock and D2O medium. The treatments by themselves were not toxic to unirradiated cells. We found that the enhanced expression of potentially lethal damage by post-treatment with caffeine or D2O medium is similar. For example, the kinetics of the repair of the potentially lethal damage expressible by either post-treatment was similar, and an additive enhancement of potentially lethal damage occurred when the two treatments were administered sequentially. These findings suggest that caffeine and D2O medium affect the same sector of potentially lethal damage. When the two treatments were combined, however, they competed with each other. That is, exposures to caffeine, which by themselves did not enhance killing (up to 1 mM for 2 h), decreased the enhanced killing due to D2O medium, Reciprocally, D2O medium reduced the enhanced killing due to high concentrations of caffeine (greater than 1 mM). Thus, although caffeine and D2O medium act on the same sector of potentially lethal damage they do so differently, suggesting that more than one pathway of the expression of radiation damage can result in the same phenotypic effect.