Radiation research
-
The effects of 60Co gamma rays on calcitonin gene-related peptide (CGRP)-immunoreactive nerve fibers and neuropeptide Y (NPY)-immunoreactive nerve fibers were examined in mesenteric blood vessels of rats. Using a free-floating immunostaining streptavidin-biotin peroxidase complex method combined with a nickel-enhancement technique, we found that the distribution pattern of these two peptidergic nerve fibers in superior mesenteric arteries and superior mesenteric veins did not change, while the densities of CGRP-immunoreactive nerve fibers and NPY-immunoreactive nerve fibers in superior mesenteric arteries and veins varied with the time after irradiation. The results suggested that CGRP and NPY may be important in the development and elimination of radiation-induced injury.
-
Suramin is a novel cytostatic/cytotoxic agent that is currently undergoing clinical trials in the treatment of hormone- and chemo-refractory tumors. Its unusual mechanism of action and its activity against prostate cancer raise the possibility that it could be particularly suitable for combined-modality treatment of prostate cancer. PC3 human prostate cancer cells were used as an in vitro model to test the possible interaction between suramin and ionizing radiation. ⋯ The effects of radiation and suramin on clonogenic cell survival appeared to be additive by isobologram analysis at clinically relevant radiation doses. Continuous exposure to a lower concentration of suramin (100 micrograms/ml) during the clonogenic assay period was as effective in decreasing clonogenic survival as 48 h exposure to 300 micrograms/ml suramin in decreasing clonogenic survival. Our data indicate that, when used in combination with radiation, suramin may be effective at concentrations that are lower than those required for efficacy as a single agent.
-
The intrinsic radiosensitivity of tumor cells is most frequently reported for asynchronous populations, although cell cycle variation in radiosensitivity is known to be significant. Linear-quadratic analyses of survival data for asynchronous human tumor cells show wide variations in the alpha coefficient with smaller variations in the beta coefficient. HT-29 (colon), OVCAR10 (ovary) and A2780 (ovary) tumor cells with alpha coefficients of 0.03, 0.16 and 0.47 Gy(-1), respectively, and square-root of beta coefficients of 0.23-0.27 Gy(-1) for asynchronous populations were amenable to synchronization by mitotic selection. ⋯ HT-29 cells remained relatively radioresistant in G2 phase. The different interphase radiosensitivities observed for these cell lines were determined mainly by the single-hit inactivation mechanism. These studies clearly demonstrate the dominant role of single-hit inactivation in determining the intrinsic radiosensitivity of human tumor cells to 137Cs gamma rays, especially at doses of 2 Gy and less.
-
There exists a growing interest in intra-operative radiation therapy as a treatment modality for large bowel cancer. In a previous experimental study we showed that high-dose intra-operative irradiation delays the healing of colonic anastomoses. However, the contribution of proteases is unknown. ⋯ After 7 days this effect had disappeared for the sham-irradiated anastomoses, but the activity in the anastomoses in both the proximal and combined groups remained significantly elevated. The findings provide evidence that intra-operative irradiation prolongs the presence of elevated gelatinolytic and collagenolytic activities in colon anastomoses. It may contribute to a reduced or delayed accumulation of collagen and other matrix proteins that supply anastomotic strength.
-
Preoperative radiotherapy as an adjunct to surgery for rectal carcinoma is generally thought to impair the healing of colorectal anastomoses. To delineate the presumed hazards of preoperative irradiation, we investigated this effect in a new model where, in contrast to experiments reported so far, anastomoses were constructed using normal tissue for the proximal limb and irradiated tissue for the distal limb. A group of 120 male Wistar rats, divided randomly into 12 groups of 10 each, were used. ⋯ Comparison between each experimental group and its control group showed that preoperative irradiation did not reduce the strength of the anastomoses. Also, the concentration and content of hydroxyproline in the tissue of the anastomoses were unchanged. These data indicate that construction of a colonic anastomosis consisting of one irradiated bowel end in rats is not by definition detrimental to the development of early wound strength.