Effects of hydralazine on in vivo tumor energy metabolism, hematopoietic radiation sensitivity, and cardiovascular parameters.
Energy metabolism of murine FSaII foot tumors was studied by in vivo 31P-MRS in C3Hf/Sed mice. Spectroscopy was performed following exposure to escalating doses of hydralazine (HYD) ip. At 0.25 mg/kg, HYD caused a 20% increase in PCr/Pi and had no significant effect on mean arterial blood pressure. HYD doses greater than or equal to 2 mg/kg lead to hypotension which was associated with a decrease in PCr, NTP, pH, and an increase in Pi (p less than 0.01 for control vs 10 mg/kg HYD). When mice were given ip injections of HYD (0.25, 1, 2 and 10 mg/kg) 10 min prior to whole body irradiation, spleen stem cell survival after 6 Gy was increased (2.19 colonies in control animals vs 6.74 colonies per spleen in animals treated with greater than or equal to 2 mg/kg HYD), as was the LD50/30 dose (6.49 Gy [control] vs 9.00 Gy [10 mg/kg HYD]). The data provide evidence that PCr/Pi is a useful indicator of perfusion efficiency (and indirectly of hypoxic cell fraction) in FSaII tumors. These observations suggest that HYD may be a useful adjuvant for hyperthermic treatment of tumors and for potentiation of agents specifically toxic to hypoxic or nutrient-deprived cancer cells. HYD should be used with care in patients receiving radiation treatments or other therapies for which hypoxia can unfavorably affect treatment outcome.
Okunieff
P
P
Department of Radiation Medicine, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Walsh
C S
CS
Vaupel
P
P
Kallinowski
F
F
Hitzig
B M
BM
Neuringer
L J
LJ
Suit
H D
HD
D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000528:radiation effects*; D006439:Hemodynamics / Q000187:drug effects*; D006830:Hydralazine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000503:physiopathology*; D011836:Radiation Tolerance / Q000187:drug effects
D006830:Hydralazine