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Oxygenation in tumors by modified hemoglobins
Author(s) -
Nozue Mutsumi,
Lee Intae,
Manning James M.,
Manning Lois R.,
Jain Rakesh K.
Publication year - 1996
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/(sici)1096-9098(199606)62:2<109::aid-jso6>3.0.co;2-c
Subject(s) - oxygenation , hemoglobin , medicine , tetramer , oxygen , hypoxia (environmental) , oxygen delivery , microbiology and biotechnology , biochemistry , chemistry , biology , organic chemistry , enzyme
The effect of systemic injection of modified hemoglobin (Hb) prepared from bovine. human, or mouse Hb on tumor oxygenation was investigated. Hb was modified by (1) diisothiocyanatobenzenesulfonate (DIBS) to yield cross‐linking within a tetramer; (2) glycolaldehyde (Glyal) to yield cross‐linking between and within tetramers; (3) carboxymethylation (Cm) to change oxygen affinity: or (4) poly(ethylene glycol) (PEG) to yield attachment between tetramers. HGL9 (human glioma) in nude mice and FSaII (mice fibrosarcoma) in C3H mice were used as tumor models. Dose and time dependency were detected in the oxygenation effect by bovine‐PEG‐Hb. Internal cross‐linkage prolonged the half‐life in the circulation, and thus showed a significant effect. Compared to bovine‐CmHb, bovine‐DIBS‐Hb and bovine‐DIBS‐CmHb were more effective. Decreasing the oxygen affinity by Cm significantly enhanced tumor oxygenation. Human‐DIBS‐CmHb was more effective than human‐DIBS‐Hb. These effects were caused by oxygen carrying capacity of modified Hbs as well as hemodynamic factors, and the injection seemed to reduce both perfusion‐limited (acute) and diffusion‐limited (chronic) hypoxia. © 1996 Wiley‐Liss, Inc.