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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 Hoechst 33342 injection dose and injection volume on hypoxic fraction measured using pimonidazole binding. (A) SCCVII tumours were injected in three tracks with 0.1 ml containing various amounts of Hoechst 33342 administered 5 min after i.p. injection of 100 mg kg−1 pimonidazole. The means and standard deviations for 3–5 tumours per dose are shown. (B) SCCVII tumours were injected in three tracks with either the same amount of Hoechst (20 ng, triangles) or the same concentration of Hoechst (1 mg ml−1, circles) in different volumes of PBS given 5 min after i.p. injection of pimonidazole. Results for individual tumours are shown. The dotted lines indicate the dose and volume used in Figures 3 and 6. Open symbols show the response of the brightest one out of six of the tumour cells and closed symbols show the response of the dimmest one out of six of the cells.
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fig7: Effect of Hoechst 33342 injection dose and injection volume on hypoxic fraction measured using pimonidazole binding. (A) SCCVII tumours were injected in three tracks with 0.1 ml containing various amounts of Hoechst 33342 administered 5 min after i.p. injection of 100 mg kg−1 pimonidazole. The means and standard deviations for 3–5 tumours per dose are shown. (B) SCCVII tumours were injected in three tracks with either the same amount of Hoechst (20 ng, triangles) or the same concentration of Hoechst (1 mg ml−1, circles) in different volumes of PBS given 5 min after i.p. injection of pimonidazole. Results for individual tumours are shown. The dotted lines indicate the dose and volume used in Figures 3 and 6. Open symbols show the response of the brightest one out of six of the tumour cells and closed symbols show the response of the dimmest one out of six of the cells.

Mentions: Hoechst 33342 is known to be vasoactive at high concentrations (Trotter et al, 1990), so intratumour injection of this drug could lead to a localized decrease in blood flow and might explain the hypoxia associated with the injection site. Alternatively, injection of a significant volume of fluid into a tumour could increase interstitial fluid pressure, leading to vascular collapse and a subsequent increase in hypoxia. To examine these possibilities, different concentrations and volumes of Hoechst 33342 were injected 5 min after i.p. administration of pimonidazole. Although there was a trend for the hypoxic fraction to increase with increasing Hoechst 33342 concentration (Figure 7aFigure 7


Local hypoxia is produced at sites of intratumour injection.

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

Effect of Hoechst 33342 injection dose and injection volume on hypoxic fraction measured using pimonidazole binding. (A) SCCVII tumours were injected in three tracks with 0.1 ml containing various amounts of Hoechst 33342 administered 5 min after i.p. injection of 100 mg kg−1 pimonidazole. The means and standard deviations for 3–5 tumours per dose are shown. (B) SCCVII tumours were injected in three tracks with either the same amount of Hoechst (20 ng, triangles) or the same concentration of Hoechst (1 mg ml−1, circles) in different volumes of PBS given 5 min after i.p. injection of pimonidazole. Results for individual tumours are shown. The dotted lines indicate the dose and volume used in Figures 3 and 6. Open symbols show the response of the brightest one out of six of the tumour cells and closed symbols show the response of the dimmest one out of six of the cells.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2375199&req=5

fig7: Effect of Hoechst 33342 injection dose and injection volume on hypoxic fraction measured using pimonidazole binding. (A) SCCVII tumours were injected in three tracks with 0.1 ml containing various amounts of Hoechst 33342 administered 5 min after i.p. injection of 100 mg kg−1 pimonidazole. The means and standard deviations for 3–5 tumours per dose are shown. (B) SCCVII tumours were injected in three tracks with either the same amount of Hoechst (20 ng, triangles) or the same concentration of Hoechst (1 mg ml−1, circles) in different volumes of PBS given 5 min after i.p. injection of pimonidazole. Results for individual tumours are shown. The dotted lines indicate the dose and volume used in Figures 3 and 6. Open symbols show the response of the brightest one out of six of the tumour cells and closed symbols show the response of the dimmest one out of six of the cells.
Mentions: Hoechst 33342 is known to be vasoactive at high concentrations (Trotter et al, 1990), so intratumour injection of this drug could lead to a localized decrease in blood flow and might explain the hypoxia associated with the injection site. Alternatively, injection of a significant volume of fluid into a tumour could increase interstitial fluid pressure, leading to vascular collapse and a subsequent increase in hypoxia. To examine these possibilities, different concentrations and volumes of Hoechst 33342 were injected 5 min after i.p. administration of pimonidazole. Although there was a trend for the hypoxic fraction to increase with increasing Hoechst 33342 concentration (Figure 7aFigure 7

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