Interference with energy production as a means of causing injury to a human pancreatic carcinoma.
The ATP content of a human pancreatic carcinoma, cultured as a xenograft in athymic nude (nu/nu) mice, dropped by 70% within 1 h of treating the hosts with hydralazine (10 mg/kg s.c.), while the energy charge fell from 0.79 to 0.53. By 24 h, the pattern of adenine nucleotides, as shown by the energy charge, had reverted to normal; meanwhile, the ATP level recovered somewhat, showing an eventual loss of 41%. A second administration (also 10 mg/kg s.c.) 23 h after the first produced no further effect on energy metabolism 1 h later, indicating that a state of drug refractoriness had been established. Losses of adenine nucleotides from the carcinoma 24 h after the initial treatment with hydralazine amounted to 37%, from which it was estimated that 35-40% necrosis could be expected from the procedure.
D000244:Adenosine Diphosphate / Q000032:analysis; D000249:Adenosine Monophosphate / Q000032:analysis; D000255:Adenosine Triphosphate / Q000032:analysis*; D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D006830:Hydralazine / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D009336:Necrosis; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology
D006830:Hydralazine; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate