The effect of recombinant human erythropoietin treatment on tumour radiosensitivity and cancer-associated anaemia in the mouse.
Recombinant human erythropoietin (rHuEpo) has recently become available for the treatment of chronic anaemia, including that associated with cancer. Carcinoma NT in CBA mice causes a progressive anaemia which can be overcome by daily injections of recombinant human erythropoietin (rHuEpo). This model was used to study the effect of haematocrit on tumour blood flow, growth rate and radiosensitivity, in mice with haematocrits ranging from approximately 38% (control) to 65% (20 U/day rHuEpo). Tumours showed a small but significant slowing in growth rate with higher haematocrit. In vitro studies showed rHuEpo had no direct effect on the growth of NT cells. Tumour blood flow was measured by two methods in each mouse (133Xe clearance and 86Rubidium uptake). Blood flow showed a tendency to decrease with increasing blood viscosity although this effect was not significant despite the large differences in haematocrit. Although tumour doubling time was prolonged despite the large differences in haematocrit. Although tumour doubling time was prolonged with increasing radiation dose, from 0 (sham irradiated) to 35 Gy, haematocrit was not found to influence the growth delay. This was attributed to adaptation of the tumour during the relatively slow change in the haematocrit. rHuEpo is being considered for clinical use in anaemic cancer patients. Our data suggest that this treatment will correct haematocrit with no effect on tumour radiosensitivity.
Joiner
B
B
CRC Gray Laboratory, Mount Vernon Hospital, Northwood, Middx, UK.
Hirst
V K
VK
McKeown
S R
SR
McAleer
J J
JJ
Hirst
D G
DG
D000740:Anemia / Q000097:blood* / Q000209:etiology; D000818:Animals; D002277:Carcinoma / Q000097:blood* / Q000098:blood supply / Q000150:complications / Q000473:pathology / Q000503:physiopathology / Q000532:radiotherapy; D002455:Cell Division / Q000187:drug effects; D004921:Erythropoietin / Q000494:pharmacology*; D006400:Hematocrit; D006801:Humans; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D011836:Radiation Tolerance; D011994:Recombinant Proteins / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects
D011994:Recombinant Proteins; D004921:Erythropoietin