Browsing All Paterson Institute for Cancer Research by Authors
Bone marrow toxicity in mice treated with indium-114m-labelled blood cells.Hoyes, Katherine P; Wadeson, P J; Murby, Brian; Sharma, Harbans L; Cowan, Richard A; Lord, Brian I; CRC Dept. of Experimental Haematology, Paterson Institute for Cancer Research, University of Manchester, UK. (2001-12)Clinical trials with autologous indium-114m-labelled lymphocytes have revealed significant anti-tumour effects in chronic lymphocytic leukaemia patients with highly resistant disease. Substitution of the lymphocyte vector with heat-damaged red blood cells (HDRBC) may make this treatment more universally applicable and reduce the dose-limiting myelosuppression encountered with labelled lymphocytes. Therefore, the bone marrow localization and toxicities of indium-labelled lymphocytes or HDRBC have been investigated in BDFI mice. At 24 hours approximately 4% and 1.2% of 114In(m) administered as labelled lymphocytes or HDRBC respectively was localized within the bone marrow and remained constant for 57 days thereafter. Toxicity towards bone marrow stem cells, measured as CFU-S, was equivalent for both cellular vectors. However, at clinically relevant activities, 114In(m) HDRBC were less toxic than labelled lymphocytes towards committed progenitors, assayed as in vitro-CFC and CFU-Meg. These data suggest that substitution of HDRBC for lymphocytes as the 114In(m) vector may be beneficial in reducing the myelosuppression associated with this technique.
Mutation studies in lacI transgenic mice after exposure to radiation or cyclophosphamide.Hoyes, Katherine P; Wadeson, P J; Sharma, Harbans L; Hendry, Jolyon H; Morris, Ian D; School of Biological Sciences and Department of Medical Biophysics, University of Manchester, UK. email@example.com (1998-11)We have used the Big Blue lacI transgenic mouse reporter system to investigate mutation induction in the testes, spleen and liver after exposure to an internally incorporated radionuclide, 114mIn, whole body irradiation with 60Co gamma-rays and systemically administered cyclophosphamide. Spontaneous mutation frequencies were 6-17x10(-6). No statistically significant mutation induction was observed in testes or spleen at 35 days after exposure to any test agent, although mutation frequencies tended to be increased (by approximately 1.5-fold) after exposure to 1 Gy gamma-rays. However, liver mutation frequencies were doubled after treatment with 100 mg/kg cyclophosphamide and were elevated by approximately 2.5-fold after systemic administration of 114mIn and 4.5-fold after 1 Gy 60Co gamma-rays. When data from all organs were pooled, mutation frequency was doubled after exposure to 1 Gy gamma-rays, but no other significant increases were observed. These findings support the hypothesis that the lacI transgenic mouse may be relatively inefficient at detecting mutations induced by exposure to ionizing radiation or other agents which produce a spectrum of deletion sizes, including those which are larger than the lacI transgene.