Local hypoxia is produced at sites of intratumour injection.
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.
Affiliation: Medical Biophysics Department, British Columbia Cancer Research Centre, 601 W 10th Avenue, Vancouver, BC, V5Z 1L3 Canada. firstname.lastname@example.orgShow MeSH
Related in: MedlinePlus
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
Affiliation: Medical Biophysics Department, British Columbia Cancer Research Centre, 601 W 10th Avenue, Vancouver, BC, V5Z 1L3 Canada. email@example.com