5-Bromo-2'-deoxyuridine incorporation into DNA in hepatic VX2 tumor-bearing rabbits.
The halogenated pyrimidine 5-bromo-2'-deoxyuridine (BrdUrd) possesses both radiosensitizing and antimetabolite effects through its incorporation as a thymidine analog in replicating DNA. To evaluate the regional advantage for treatment of hepatic malignancy by hepatic arterial infusion, BrdUrd was infused into either the hepatic artery (HA) or a central vein (iv) in 26 rabbits with intrahepatic VX2 tumor. After a 24-hr constant rate infusion of 10, 20, or 40 mg/kg/24 hr, the percentage BrdUrd incorporation into the DNA of bone marrow, duodenal mucosa, liver, and hepatic VX2 tumor was measured by gas chromatography/mass spectrometry methods. VX2 tumor BrdUrd incorporation was greater by HA than by iv routes (P less than 0.001). At doses of 10 and 20 mg/kg/day, HA to iv BrdUrd incorporation ratios for VX2 tumor significantly exceeded those for bone marrow and duodenum (P less than 0.05). At appropriate dose rates, hepatic arterial administration of BrdUrd provides a regional advantage for DNA BrdUrd incorporation in the rabbit intrahepatic VX2 tumor.
Department of Surgery, University of Michigan Medical Center, Ann Arbor.
J A
JA
Knol
P L
PL
Stetson
J G
JG
Wagner
N J
NJ
Johnson
Z M
ZM
Yang
D
D
Prieskorn
P
P
Terrio
C A
CA
Knutsen
W D
WD
Ensminger
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000008:administration & dosage / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002849:Chromatography, Gas; D004247:DNA / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000378:metabolism*; D004386:Duodenum / Q000378:metabolism; D006499:Hepatic Artery; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D007413:Intestinal Mucosa / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism*; D013058:Mass Spectrometry; D009368:Neoplasm Transplantation; D011817:Rabbits; D014683:Vena Cava, Superior
D004273:DNA, Neoplasm; D004247:DNA; D001973:Bromodeoxyuridine