Comparison of tumour age response to radiation for cells derived from tissue culture or solid tumours

Abstract

Summary Direct comparison of the cell age response of 9L and KHT tumour cells derived either from tissue culture or solid tumours was achieved. Cells from dissociated KHT and 9L tumours (the latter implanted either subcutaneously or intracerebrally) and cells from tissue culture were separated into homogenous sized populations by centrifugal elutriation. In both tumour models these homogeneous sized populations correspond to populations enriched at different stages of the cell cycle. The survival of these elutriated cell populations was measured after a single dose of Cs-137 gamma rays. For cells isolated from 9L solid tumours, there was little variation in radiosensitivity throughout the cell cycle; however, a very small but significant increase in resistance was found in late G, cells. This lack of a large variation in radiosensitivity through the cell cycle for 9L cells from solid tumours also was seen in 9L cells growing in monolayer tissue culture. When similar experiments were performed using the KHT sarcoma tumour model, the results showed that KHT cells in vitro exhibited a fairly conventional increase in radioresistance in both mid G, and late S. However, the cell age response of KHT cells from solid tumours was different; particularly in the late S and G2 + M phases. These data demonstrate that direct extrapolation of in vitro cell age responses to the in situ situation may not always be valid.

Hypoxia-regulated p53 and its effect on radiosensitivity in cancer cells

“…In general cellular radiation resistance increases during S phase and reaches maximum in the latter part of S phase (Pawlik & Keyomarsi 2004), however, Keng et al (1984) reported that in KHT-C cells the late G1 population was slightly less radiosensitive than cells from other cell cycle stages, therefore hypoxia-induced enrichment of the G1 population might be a reason for increased radiation resistance in hypoxic KHT-C cells. However, our data in Figure 3 indicated that enrichment of the G1 population by Table I.…”

“…This is confirmed in all of the three tumor cell lines being used for this study, in which we observed the enrichment of the G1 population after hypoxia treatment ( Figure 3A). Although late S phase cells are generally considered as the least radiosensitive cell population (Pawlik & Keyomarsi 2004), it has also been reported that in KHT-C cells late G1 population is the least radiosensitive (Keng et al 1984).…”

Characterization of radiation resistant hypoxic cell subpopulations in KHT sarcomas. (ii) Cell sorting

“…This is because in the KHT sarcoma, there is little difference between the radiation sensitivity of the most resistant S and G1 cell subpopulations Keng et al, 1984) i.e., the cell subpopulations which dominate the dimmest and brightest sort fractions. However, when Hoechst 33342 sorting is used to study hypoxic subpopulations in other tumour models, differences in the cell cycle distributions in the sorted fractions may need to be considered when interpreting the results.…”

Effects on Lung Tissue After Breast Cancer Radiation: Comparing Photon and Proton Therapies

“…There have been many eloquent studies of the radiation dose-response relationship (“dose-response”) of lung tissue aimed to better understand the underlying radiobiology 2 and to model 24 the radiation delivery effects of regional dose magnitude, dose rate, dose volume, fractionation schedule, and type of radiation, 25 among others. Historically, these studies measured rates of cell 26 or animal death 27 and, more recently, have focused on subclinical changes in pixel-wise density observed with chest CT. 28 While analysis of dose-response has important clinical implications, here we sought to answer whether PT is safer (causes less overall lung tissue damage) than photon therapy, given the differences in the underlying radiobiology and modern radiation delivery for each modality. For this objective, total tissue reaction is the more relevant metric.…”