Oxygen dependence of binding of misonidazole to rodent and human tumors in vitro - PubMed (original) (raw)

. 1987 Oct 15;47(20):5367-76.

Affiliations

PMID: 3652041

Oxygen dependence of binding of misonidazole to rodent and human tumors in vitro

A J Franko et al. Cancer Res. 1987.

Abstract

Misonidazole, a 2-nitroimidazole, has been shown to form metabolically induced adducts to cellular molecules at a very high rate in the absence of oxygen, and this rate decreases substantially as the oxygen concentration increases. Thus, it has considerable potential as a marker for hypoxic, radiation resistant cells in tumors. The dependence of the rate of adduct formation (binding) on oxygen concentration was studied for EMT6/Ed, Walker 256, and Dunning R3327-AT rodent tumors and for two human colon carcinomas, a human melanoma, and a human breast carcinoma. Fragments of these tumors were incubated with [14C]- or [3H]misonidazole in vitro at several oxygen concentrations and the quantity of misonidazole bound was determined from autoradiographs as a function of distance from the surfaces of the fragments. The Km of binding inhibition (oxygen concentration for half-maximal binding) for the tumors varied by a factor of 10. The range was centered on the range of values reported for the Km of cellular radioresistance (oxygen concentration for half-maximal radioresistance). The patterns of binding at depth within the tumor fragments indicated that gradients of cellular waste products and nutrients other than oxygen had minimal effects on binding. All tumors were capable of metabolizing oxygen to levels sufficiently low to yield the maximal binding rate, but the distance of penetration of oxygen varied, indicating a range of at least 4 in rates of oxygen consumption. The ratio of misonidazole bound by stromal tissue versus tumor cells ranged from 0.9 for a colon tumor to 0.3 for a breast tumor. These properties of misonidazole binding indicate that it should be a good marker for radiobiological hypoxia in tumors, providing adequate controls can be performed.

PubMed Disclaimer

Cited by

Hypoxia imaging and radiotherapy: bridging the resolution gap.
Grimes DR, Warren DR, Warren S. Grimes DR, et al. Br J Radiol. 2017 Aug;90(1076):20160939. doi: 10.1259/bjr.20160939. Epub 2017 May 25. Br J Radiol. 2017. PMID: 28540739 Free PMC article. Review.
Identification of hypoxia in cells and tissues of epigastric 9L rat glioma using EF5 [2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl) acetamide].
Evans SM, Joiner B, Jenkins WT, Laughlin KM, Lord EM, Koch CJ. Evans SM, et al. Br J Cancer. 1995 Oct;72(4):875-82. doi: 10.1038/bjc.1995.427. Br J Cancer. 1995. PMID: 7547234 Free PMC article.
The relationship between tumour oxygenation determined by oxygen electrode measurements and magnetic resonance spectroscopy of the fluorinated 2-nitroimidazole SR-4554.
Aboagye EO, Maxwell RJ, Horsman MR, Lewis AD, Workman P, Tracy M, Griffiths JR. Aboagye EO, et al. Br J Cancer. 1998;77(1):65-70. doi: 10.1038/bjc.1998.10. Br J Cancer. 1998. PMID: 9459147 Free PMC article.
Detection of hypoxic cells in a C3H mouse mammary carcinoma using the comet assay.
Olive PL, Horsman MR, Grau C, Overgaard J. Olive PL, et al. Br J Cancer. 1997;76(6):694-9. doi: 10.1038/bjc.1997.448. Br J Cancer. 1997. PMID: 9310232 Free PMC article.

Oxygen dependence of binding of misonidazole to rodent and human tumors in vitro - PubMed (original) (raw)