Parallel comparison of pre-conditioning and post-conditioning effects in human cancers and keratinocytes upon acute gamma irradiation

Abstract

Purpose: To determine and compare the effects of pre-conditioning and post-conditioning towards gamma radiation responses in human cancer cells and keratinocytes.

Material and methods: The clonogenic survival of glioblastoma cells (T98G), keratinocytes (HaCaT), and colorectal carcinoma cells (HCT116 p53^+/+ and p53^−/−) was assessed following gamma ray exposure from a Cs-137 source. The priming dose preceded the challenge dose in pre-conditioning whereas the priming dose followed the challenge dose in post-conditioning. The priming dose was either 5 mGy or 0.1 Gy. The challenge dose was 0.5–5 Gy.

Results: In both pre- and post-conditioning where the priming dose was 0.1 Gy and the challenge dose was 4 Gy, RAR developed in T98G but not in HaCaT cells. In HCT116 p53^+/+, pre-conditioning had either no effect or a radiosensitizing effect and whereas post-conditioning induced either radiosensitizing or radioadaptive effect. The different observed outcomes were dependent on dose, the time interval between the priming and challenge dose, and the time before the first irradiation. Post-conditioning effects could occur with a priming dose as low as 5 mGy in HCT116 p53^+/+ cells. When HCT116 cells had no p53 protein expression, the radiosensitizing or radioadaptive response by the conditioning effect was abolished.

Conclusions: The results suggest that radiation conditioning responses are complex and depend on at least the following factors: the magnitude of priming/challenge dose, the time interval between priming and challenge dose, p53 status, cell seeding time prior to the first radiation treatment. This work is the first parallel comparison demonstrating the potential outcomes of pre- and post-conditioning in different human cell types using environmentally and medically relevant radiation doses.

Keywords:

• Cancer
• p53
• pre-conditioning
• post-conditioning
• gamma radiation

Acknowledgments

The authors kindly acknowledge Scott McMaster (McMaster University) for assistance with the use of the irradiation facility as well as dose uniformity analysis. The authors also acknowledge Dr. Cristian Fernandez-Palomo for his cultivation of T98G and passing this line to us.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The authors acknowledge support from the Canada Research Chairs program, the National Science and Engineering Research Council (NSERC) Collaborative Research and Development program, and NSERC Discovery Grants program.