QUANTITATIVE OBSERVATIONS OF THE ACUTE EFFECTS OF X-IRRADIATION ON BRAIN CAPILLARY-PERMEABILITY .1.

Rats were irradiated with single and multiple dally dose fractions of 200-2500 rad; the capillary permeability coefficients (P) for 14C-urea, 3H-galactitol, 3H-VM-26, and bleomycin were determined after completion of each course. The drugs have a wide range of molecular weights and lipophilicities. Radiation doses of 200 rad × 5 days and 400 rad × 1 day increased the urea P 14-32%, while other dose fractions had no effect on P. The P for galactitol was increased more consistently (52-116%) by single and multiple 200 rad fractions and single fractions of 400 and 1000 rad. The P for galactitol paradoxically was reduced approximately 60% by 200 rad × 10 days and 2500 rad × 1 day fractions. Permeability to galactitol was determined at various times 3-24 hr after single radiation doses of 200, 400, and 1000 rad; at all times P was increased over nonirradiated animals. No radiation dose had an effect on the P for bleomycin. Except for a single fraction (400 rad × 1 day), the P for VM-26 was also unaffected by radiation, and in that instance the P was reduced from normal. We conclude that the radiation fractions used in these studies produced little acute effect on the permeability of normal brain capillaries to the antitumor antibiotic bleomycin, the large lipophilic podophyllotoxin derivative VM-26, and urea, a small nonionized hydrophilic molecule. The only consistent increase in P occurred with galactitol, a hydrophilic molecule (molecular weight of 182 Daltons) that is normally quite restricted in its transcapillary transit in the brain. © 1979.