Blood flow modification by nicotinamide and metoclopramide in mouse tumours growing in different sites.
Nicotinamide (NA) and metoclopramide (MCA) have been shown to be sensitisers of the effects of radiation and drugs in experimental rodent tumours growing in skin and muscle. We have used 86Rb uptake to investigate the effects of these two drugs on the distribution of blood to a mouse carcinoma (NT) growing in skin, muscle or the gut wall, as well as to the host normal tissue. NA caused an increase in cardiac output distribution (COD) of between 17 and 92% to tumours in the three sites. When this increase is related to the changes in COD to the host normal tissues, however, COD to tumours in skin and muscle was increased by a factor of 1.8 and to tumours in the gut wall by a factor of 1.7. MCA caused a consistent increase in COD to tumours growing in muscle, but the effects in tumours in skin and gut were variable with time. Again when related to the change in COD to host normal tissues, a factor of 2.1 was seen for COD to tumours growing in muscle and gut. Both NA and MCA alter COD to tumours in some sites relative to host tissues in a way that could enhance anti-cancer drug delivery to tumours, though the effects of NA are more reliable in our systems.
Hirst
D G
DG
CRC Gray Laboratory, Mount Vernon Hospital, Northwood, Middx. UK.
Joiner
B
B
Hirst
V K
VK
D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D003110:Colonic Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy / Q000503:physiopathology; D008787:Metoclopramide / Q000494:pharmacology*; D051379:Mice; D008808:Mice, Inbred CBA; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000098:blood supply*; D009536:Niacinamide / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D014183:Transplantation, Heterologous
D009536:Niacinamide; D008787:Metoclopramide