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Local hypoxia is produced at sites of intratumour injection.

Olive PL, Luo CM, Banáth JP - Br. J. Cancer (2002)

Bottom Line: Hoechst-labelled cells sorted from these tumours were more sensitive to killing by hypoxic cell cytotoxins (tirapazamine, RSU-1069) and less sensitive to damage by ionizing radiation.Hoechst-labelled cells also bound the hypoxia marker pimonidazole when given by i.p. injection.This effect could have significant implications for intratumour injection of drugs, cytokines or vectors that are affected by the oxygenation status of the tumour cells as well as potential effects on biodistribution via local microvasculature.

View Article: PubMed Central - PubMed

Affiliation: Medical Biophysics Department, British Columbia Cancer Research Centre, 601 W 10th Avenue, Vancouver, BC, V5Z 1L3 Canada. polive@bccancer.bc.ca

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Effect of ionizing radiation on survival of cells lining the needle track. Tumours were injected with 20 ng Hoechst 33342 in 0.1 ml. Five minutes to 20 h later, tumours were exposed to 10 Gy X-rays and subsequently excised. Single cells were sorted based on Hoechst 33342 concentration into six fractions and plated for colony formation. The relative clonogenic survival of the brightest cells compared to the dimmest cells of the tumour is plotted as a function of time of irradiation after Hoechst injection. The mean and standard deviation for five tumours is shown. Note that when Hoechst 33342 is given by i.t. injection after irradiation (▵), there is no distinction between the sensitivity of the dimmest and brightest cells. ** Indicate values significantly different from the response when irradiation is given post-injection.
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fig3: Effect of ionizing radiation on survival of cells lining the needle track. Tumours were injected with 20 ng Hoechst 33342 in 0.1 ml. Five minutes to 20 h later, tumours were exposed to 10 Gy X-rays and subsequently excised. Single cells were sorted based on Hoechst 33342 concentration into six fractions and plated for colony formation. The relative clonogenic survival of the brightest cells compared to the dimmest cells of the tumour is plotted as a function of time of irradiation after Hoechst injection. The mean and standard deviation for five tumours is shown. Note that when Hoechst 33342 is given by i.t. injection after irradiation (▵), there is no distinction between the sensitivity of the dimmest and brightest cells. ** Indicate values significantly different from the response when irradiation is given post-injection.

Mentions: Since the drug concentration was highest in cells along the track of the needle, one could argue that more damage occurred here simply because these cells were exposed to the highest drug dose. Therefore, response to ionizing radiation, which produces three times more killing in aerobic than hypoxic cells, was also used to determine whether cells bordering the needle track were hypoxic. Tumours that had been injected with Hoechst 5 min before exposure to radiation showed less killing of the brightly fluorescent cells compared to the dimmest cells (Figure 3Figure 3


Local hypoxia is produced at sites of intratumour injection.

Olive PL, Luo CM, Banáth JP - Br. J. Cancer (2002)

Effect of ionizing radiation on survival of cells lining the needle track. Tumours were injected with 20 ng Hoechst 33342 in 0.1 ml. Five minutes to 20 h later, tumours were exposed to 10 Gy X-rays and subsequently excised. Single cells were sorted based on Hoechst 33342 concentration into six fractions and plated for colony formation. The relative clonogenic survival of the brightest cells compared to the dimmest cells of the tumour is plotted as a function of time of irradiation after Hoechst injection. The mean and standard deviation for five tumours is shown. Note that when Hoechst 33342 is given by i.t. injection after irradiation (▵), there is no distinction between the sensitivity of the dimmest and brightest cells. ** Indicate values significantly different from the response when irradiation is given post-injection.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2375199&req=5

fig3: Effect of ionizing radiation on survival of cells lining the needle track. Tumours were injected with 20 ng Hoechst 33342 in 0.1 ml. Five minutes to 20 h later, tumours were exposed to 10 Gy X-rays and subsequently excised. Single cells were sorted based on Hoechst 33342 concentration into six fractions and plated for colony formation. The relative clonogenic survival of the brightest cells compared to the dimmest cells of the tumour is plotted as a function of time of irradiation after Hoechst injection. The mean and standard deviation for five tumours is shown. Note that when Hoechst 33342 is given by i.t. injection after irradiation (▵), there is no distinction between the sensitivity of the dimmest and brightest cells. ** Indicate values significantly different from the response when irradiation is given post-injection.
Mentions: Since the drug concentration was highest in cells along the track of the needle, one could argue that more damage occurred here simply because these cells were exposed to the highest drug dose. Therefore, response to ionizing radiation, which produces three times more killing in aerobic than hypoxic cells, was also used to determine whether cells bordering the needle track were hypoxic. Tumours that had been injected with Hoechst 5 min before exposure to radiation showed less killing of the brightly fluorescent cells compared to the dimmest cells (Figure 3Figure 3

Bottom Line: Hoechst-labelled cells sorted from these tumours were more sensitive to killing by hypoxic cell cytotoxins (tirapazamine, RSU-1069) and less sensitive to damage by ionizing radiation.Hoechst-labelled cells also bound the hypoxia marker pimonidazole when given by i.p. injection.This effect could have significant implications for intratumour injection of drugs, cytokines or vectors that are affected by the oxygenation status of the tumour cells as well as potential effects on biodistribution via local microvasculature.

View Article: PubMed Central - PubMed

Affiliation: Medical Biophysics Department, British Columbia Cancer Research Centre, 601 W 10th Avenue, Vancouver, BC, V5Z 1L3 Canada. polive@bccancer.bc.ca

Show MeSH
Related in: MedlinePlus