Marking hypoxic cells for complement and cytotoxic T lymphocyte-mediated lysis: using pimonidazole.

Artificial antigens are created when 2-nitroimidazoles bind to hypoxic cells. These antigens have been used in the immunodetection of tumour hypoxia but they might also serve to stimulate immune lysis of hypoxic tumour cells by complement- and cell-mediated processes. In order to test this hypothesis, lymphocytes isolated from the spleens of C3H/HeN mice that had been immunised with pimonidazole-labelled 3152-PRO cells were subcultured and tested for their ability to lyse chromium-51 loaded, pimonidazole-labelled 3152-PRO cells in an in vitro assay. In a parallel study, commercially available, rabbit complement was tested for its ability to lyse pimonidazole-labelled V79-4 cells in the presence of monoclonal antibodies which recognise protein adducts of reductively activated pimonidazole. Complement-mediated cell lysis was measured by means of an MTT assay. Complement-mediated and cell-mediated lysis was observed at pimonidazole concentrations which, in themselves, do not produce cell killing.

[1]  G. Arteel,et al.  Evidence that hypoxia markers detect oxygen gradients in liver: pimonidazole and retrograde perfusion of rat liver. , 1995, British Journal of Cancer.

[2]  G. Rosner,et al.  Distribution of the hypoxia marker CCI-103F in canine tumors. , 1994, International journal of radiation oncology, biology, physics.

[3]  D. Thrall,et al.  ELISA quantification of CCI-103F binding in canine tumors prior to and during irradiation. , 1994, International journal of radiation oncology, biology, physics.

[4]  D. Thrall,et al.  An enzyme-linked immunosorbent assay for hypoxia marker binding in tumours. , 1994, British Journal of Cancer.

[5]  W. Kast,et al.  Potential immunogenicity of oncogene and tumor suppressor gene products. , 1993, Current opinion in immunology.

[6]  R. Jain,et al.  Pharmacokinetic analysis of the perivascular distribution of bifunctional antibodies and haptens: comparison with experimental data. , 1992, Cancer research.

[7]  C. Koch,et al.  Importance of thiols in the reductive binding of 2-nitroimidazoles to macromolecules. , 1990, Biochemical pharmacology.

[8]  D. Thrall,et al.  Immunohistochemical detection of a hypoxia marker in spontaneous canine tumours. , 1990, British Journal of Cancer.

[9]  W. Ptak,et al.  Contrasuppression and tumor rejection. , 1987, Immunology letters.

[10]  James B. Mitchell,et al.  Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing. , 1987, Cancer research.

[11]  J. D. Chapman,et al.  Characteristics of the metabolism-induced binding of misonidazole to hypoxic mammalian cells. , 1983, Cancer research.

[12]  C. Hardy,et al.  The Chemistry of Nitroimidazole Hypoxic Cell Radiosensitizers , 1982 .

[13]  J. Raleigh,et al.  Nitroreductase-induced binding of nitroaromatic radiosensitizers to unsaturated lipids. Nitroxyl adducts. , 1981, Biochemical pharmacology.