This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kamen, B. A. Articles by Holcenberg, J. S. Search for Related Content PubMed PubMed Citation Articles by Kamen, B. A. Articles by Holcenberg, J. S.

Effects of Single-Dose and Fractionated Cranial Irradiation on Rat Brain Accumulation of Methotrexate

Departments of Pharmacology [B. A. K., J. S. H., B. J. R., S. M. A.] and Radiation Oncology [J. E. M., L. E. K., B. L. F.], Medical College of Wisconsin, Milwaukee, Wisconsin 53226

The effects of single-dose and fractionated whole-brain irradiation on brain methotrexate (MTX) has been studied in a rat model. The amount of MTX present in the brain 24 hr after a single i.p. dose (100 mg/kg) was the same whether animals were sham irradiated or given a single dose of 2000 rads 6 or 48 hr prior to the drug (6.9, 8.3, and 6.8 pmol MTX/g, wet weight, respectively). Animals sham irradiated or given 2000 rads in 10 fractions over 11 days and treated with an average dose of 1.2 mg MTX/kg i.p. twice a week for 24 weeks did not differ significantly in their brain MTX concentration (7.9 and 8.3 pmol MTX/g, wet weight, respectively). Chronically MTX-treated animals became folate deficient whether they were irradiated or not (450 and 670 pmol folate/g, wet weight, brain in MTX-treated and control animals). Thus, MTX accumulates in the brain with acute or chronic administration, and this accumulation is not altered by this amount of brain irradiation.

¹ Supported by American Cancer Society Grant CH228 and Leukemia Society of America. To whom requests for reprints should be addressed, at Department of Pediatrics, The University of Texas Health Science Center at Dallas, 5323 Harry Hines Blvd., Dallas, TX 75235.

² Supported by National Cancer Institute Grant CA 34840. Present address: Department of Pediatrics, University of Southern California, Los Angeles Children's Hospital, Los Angeles, CA.

Received 4/30/84. Accepted 7/30/84.