The authors have previously reported that intracarotid infusion of 5 micrograms
leukotriene C4 (
LTC4) selectively increases blood-
tumor barrier permeability in rat RG-2
tumors. In this study, rats harboring RG-2
tumors were given 15-minute intracarotid infusions of
LTC4 at concentrations ranging from 0.5 microgram to 50.0 micrograms (seven rats in each dose group). Blood-
tumor and blood-brain barrier permeability were determined by quantitative autoradiography using 14C aminoisobutyric
acid. The transfer constant for permeability (Ki) within the
tumors was increased twofold by
LTC4 doses of 2.5, 5.0, and 50.0 micrograms compared to vehicle alone (90.00 +/- 21.14, 92.68 +/- 15.04, and 80.17 +/- 16.15 vs. 39.37 +/- 6.45 microliters/gm/min, respectively; mean +/- standard deviation; p less than 0.01). No significant change in Ki within the
tumors was observed at the 0.5-microgram
LTC4 dose. Blood-brain barrier permeability was selectively increased within the
tumors. At no dose in this study did
leukotrienes increase permeability within normal brain. To determine the duration of increased opening of the blood-
tumor barrier by
LTC4 administration, Ki was measured at 15, 30, and 60 minutes after termination of a 15-minute
LTC4 infusion (seven rats at each time point). The mean Ki value was still high at 15 minutes (92.68 +/- 15.04 microliters/gm/min), but declined at 30 minutes (56.58 +/- 12.50 microliters/gm/min) and 60 minutes (55.40 +/- 8.10 microliters/gm/min) after the end of
LTC4 infusion. Sulfidopeptide
leukotrienes LTC4,
LTD4,
LTE4 and
LTF4 were infused to compare their potency in opening the blood-
tumor barrier. The mean
leukotriene E4 was the most potent, increasing the permeability value 3 1/2-fold compared with vehicle alone (139.86 +/- 23.95 vs. 39.37 +/- 6.45 microliters/gm/min).