Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 83 (4), 410-4

Radiosensitization and Hypoxic Cell Toxicity of NLA-1 and NLA-2, Two New Bioreductive Compounds

Affiliations

Radiosensitization and Hypoxic Cell Toxicity of NLA-1 and NLA-2, Two New Bioreductive Compounds

M V Papadopoulou et al. Jpn J Cancer Res.

Abstract

Two new bioreductive compounds, 9-[3-(2-nitro-1-imidazolyl)propylamino]acridine hydrochloride (NLA-1) and 9-[2-(2-nitro-1-imidazolyl)ethylamino]acridine hydrochloride (NLA-2), have been prepared. They feature an acridine ring to intercalate with DNA, a 2-nitroimidazole ring as the radiosensitizing moiety and an amino functionality for increased DNA-binding and hydrophilicity. Time and concentration dependent cytotoxicity as well as radiosensitization efficacy of the two compounds under hypoxic or aerobic conditions were determined in vitro using V-79 cells and an MTT colorimetric or clonogenic assay. The isosensitization point (ISP), defined as that drug concentration which results in the same survival decrement upon exposure of hypoxic or oxygenated cells to a given radiation dose, has been determined for both compounds at 7.5 Gy and the values are significantly lower than the ISPs of 5-[3-(2-nitro-1-imidazolyl)propyl]phenanthridinium bromide, 2-(2-nitro-1-imidazolyl)ethylamine or misonidazole (MISO). NLA-1 and NLA-2 are potent hypoxic cytotoxins and on a concentration basis, more potent than MISO as radiosensitizers in vitro. The sensitization enhancement ratios were significantly increased when 1 h drug preincubation under hypoxia at 37 degrees C was applied, before irradiation at room temperature.

Similar articles

See all similar articles

Cited by 2 PubMed Central articles

References

    1. ) Brown J. M.Keynote address: Hypoxic cell radio‐sensitizers, where next ? Int. J. Radiat. Oncol. Biol. Phys. , 16 , 987 – 993 ( 1989. ). - PubMed
    1. ) Nias A. H. W.Radiation and platinum‐drug interaction — review . Int. J. Radiat. Biol , 48 , 297 – 314 ( 1985. ). - PubMed
    1. ) Stratford M. R. L. , Dennis M. F. , Watts M. E. , Watfa R. R. and Woodcock M.Radiosensitizer‐DNA interactions in relation to intracellular uptake . Int. J. Radiat. Oncol. Biol. Phys. , 16 , 1007 – 1010 ( 1989. ). - PubMed
    1. ) Adams G. E. , Ahmed L , Sheldon P. W. and Stratford I. J.RSU‐1069, a 2‐nitroimidazole containing an alkylating group: high efficiency as a radio‐ and chemosensitizer in vitro and in vivo . Int. J. Radiat. Oncol. Biol. Phys. , 10 , 1653 – 1656 ( 1984. ). - PubMed
    1. ) Chan P. K. L. , Skov K. A. , James B. R. and Farrell N. P.A new ruthenium radiosensitizer: RuCl2(DMSO)2‐(4‐nitroimidazole)2‐ Int . J. Radiat. Oncol. Biol. Phys. , 12 , 1059 – 1062 ( 1986. ). - PubMed

Publication types

LinkOut - more resources

Feedback