The effect of dexamethasone on the uptake of cisplatin in 9L glioma and the area of brain around tumor.
The negative influence of dexamethasone (Dex) on the uptake of cisplatin in brain tumors was investigated in rats bearing 9L glioma. Dex or saline was given intraperitoneally prior to intravenous administration of cisplatin 5 mg/kg. Total Platinum (Pt) concentration was quantified with atomic absorption spectroscopy (AAS) in tumor, brain around tumor (BAT), normal brain and plasma. In the second experiment DNA-adducts of cisplatin were determined in tumor and BAT by AAS. In tumor, there was no difference in the Pt concentration and in the DNA-adduct level between the two treatment groups. In BAT, the Pt level in the Dex group was 0.20 microg/g (SD=0.10 microg/g), which was significantly lower than in the controls (0.53 microg/g (SD=0.21 microg/g); p < 0.001). In addition, the DNA-adduct level in BAT was 23% lower in the Dex treated rats (p=0.05). In normal brain the Pt concentration was 10-fold lower than in tumor tissue. Thus, Dex did not significantly limit the uptake of cisplatin in brain tumor nor did it influence the uptake in normal brain parenchyma. In contrast, in BAT that has a partially disrupted BBB, the concentrations of Pt and DNA-adduct formation were significantly decreased following pretreatment with Dex. The influence of Dex on limiting the effects of chemotherapy for brain tumors needs further study.
Straathof
C S
CS
Department of Neuro-oncology, Dr. Daniel den Hoed Cancer Center and University Hospital Rotterdam, The Netherlands.
van den Bent
M J
MJ
Ma
J
J
Schmitz
P I
PI
Kros
J M
JM
Stoter
G
G
Vecht
C J
CJ
Schellens
J H
JH
D000818:Animals; D001921:Brain / Q000378:metabolism*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D002945:Cisplatin / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*; D018736:DNA Adducts / Q000187:drug effects / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D007274:Injections, Intraperitoneal; D008297:Male; D009368:Neoplasm Transplantation; D010984:Platinum / Q000097:blood / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D018736:DNA Adducts; D010984:Platinum; D003907:Dexamethasone; D002945:Cisplatin