Oxygenation in tumors by modified hemoglobins

✍ Scribed by Nozue, Mutsumi; Lee, Intae; Manning, James M.; Manning, Lois R.; Jain, Rakesh K.

• Book ID: 102646018
• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 515 KB
• Volume: 62
• Category: Article
• ISSN: 0022-4790
• DOI: 10.1002/(sici)1096-9098(199606)62:2<109::aid-jso6>3.0.co;2-c

✦ Synopsis

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 crosslinking between and within tetramers; (3) carboxymethylation (Cm) to change oxygen affinity; or (4) poly(ethy1ene 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 effccts were caused by oxygen carrying capacity of modified Hbs as well as hernodynamic factors, and the injection seemed to reduce both perfusionlimited (acute) and diffusion-limited (chronic) hypoxia.