Heterogeneity in the Development of Apoptosis in Irradiated Murine Tumours of Different Histologies

Abstract

Fifteen different murine tumours were evaluated with respect to the degree of apoptosis development that occurs in the tumour tissue in the first few hours following irradiation in vivo. Animals were killed at 3 or 6 h following irradiation with 0, 2.5, 10 or 25 Gy. Apoptosis was scored as percent aberrant nuclei by microscopic examination of histological sections made from the tumour specimens. Results showed that three of four mammary adenocarcinomas, one ovarian adenocarcinoma, and one lymphoma displayed at least 10% apoptotic cells after 25 Gy, whereas five sarcomas, three squamous cell carcinomas, and a hepatocarcinoma did not. The time courses and dose responses were similar in those tumours that responded. These data were compared with the known response of these same tumours when analysed using conventional assays. The tumours that did respond by significant apoptosis had longer specific growth delays and lower TCD50 (dose to cure 50% of animals) doses, thus suggesting that an acute apoptotic response following irradiation may be a feature of certain tumours that respond well to irradiation. Additionally, this analysis revealed heterogeneity in the apoptotic response both within an individual tumour specimen and among different tumour types. These observations of intra and intertumour heterogeneity are consistent with the idea that the propensity for apoptosis in tumours is genetically regulated.

Phase I study of vinorelbine and paclitaxel by 3‐hour simultaneous infusion with and without granulocyte colony‐stimulating factor support in metastatic breast carcinoma

“…62 Paclitaxel-induced apoptosis may be p53-dependent; 63,64 tumors that lack p53 or have a mutant form of the gene are resistant. 65,66 The apoptotic activity of vinorelbine appears to be p53-independent. 67 Cellular resistance to vinorelbine, as with other vinca alkaloids, may be caused by p-glycoprotein-mediated multidrug resistance (MDR) mechanisms.…”

Lack of ceramide generation in TF-1 human myeloid leukemic cells resistant to ionizing radiation

“…IR-induced cell death has been associated with the induction of apoptosis which is generally correlated with radiosensitivity (Meyn et al, 1993;Ling et al, 1994). However, as our study shows, a defective apoptotic response to IR may not have significant consequences in terms of IR-induced cytotoxicity above a certain threshold dose.…”

“…In fact, the inductibility of apoptosis by IR is generally correlated with radiosensitivity (Meyn et al, 1993;Ling et al, 1994). In contrast to mitotic cell death, apoptosis is a relatively rapid and irreversible process which occurs within a few hours following IR exposure.…”

Ionizing Radiation Down-regulates p53 Protein in Primary Egr-1−/− Mouse Embryonic Fibroblast Cells Causing Enhanced Resistance to Apoptosis

“…Apoptosis has also been reported in a variety of experimental tumor systems following exposure to radiation (2,3). Ionizing radiation alters the expression of specific genes, the products of which may contribute to the events leading to apoptotic cell death.…”