Increased Opening of Blood-tumour Barrier by Leukotriene C4 is Dependent on Size of Molecules

Intracarotid injections of leukotriene C4 (LTC4) will increase blood-tumour barrier (BTB) permeability for 14C aminoisobutyric acid (AIB) in RG-2 tumours in rats. In this study, rats with RG-2 tumours were given 15 minute intracarotid infusions of LTC4 (5 micrograms total dose). Blood-tumour and BBB permeability were determined by quantitative autoradiography using different sized 14C tracers; AIB (103.1 daltons, radius = 2.8 A), Sucrose (342 daltons, radius = 5 A), Inulin (5000 daltons, radius = 15 A) and Dextran (70,000 daltons, radius = 60 A), respectively (n = 7 in each group). Permeability (Ki) within tumours for AIB, Sucrose and Inulin increased significantly after LTC4 infusion (92.7 +/- 15.0 vs 39.4 +/- 6.5, 47.8 +/- 5.2 vs 29.1 +/- 8.8, and 46.4 +/- 8.4 vs 26.4 +/- 4.8 microliters/gm/min, respectively, p < 0.01) (mean +/- SD). No significant change in Ki for 14C Dextran was observed. Increased permeability within tumours after LTC4 infusion is dependent on molecular size. This suggests that LTC4 opens tight junctions rather than increases vesicular transport through endothelial cells.