Abrin toxin

Funatsu, G., Funatsu, M. (1970). Isolation and chemical properties of various types of ricin. Jpn. J. Med. Sci. Biol. 23 342-4 Gareth, D., Griffiths, G.D., Rice, P., Allenby, A.C., Bailey, S.C., Upshall, D.G. (1995). Inhalation toxicology and histopa-thology of ricin and abrin toxins. Inhal. Toxicol. 7 269-88 Gill, D.M. (1982). Bacterial toxins a table of lethal amounts. Microbiol. Rev. 46 86-94. 

Griffiths, D., Rice, P., Allenby, A.C., Bailey, S.C. and Upshall, D.G. (1995a) Inhalation toxicology and histopathology of ricin and abrin toxins. Inhal Toxicol, 7, 269-288. 

Tang, J., Yu, T., Guo, L., Xie, J., Shao, N., He, Z. (2007a). In vitro selection of DNA aptamer against abrin toxin and aptamer-based abrin direct detection. Biosens Bioelectron 22, 2456-2463. 

K Sandvig, S Olsnes. (1982). Entry of toxic proteins abrin, modeccin, ricin, and diphtheria toxin into cells. I. Requirement for Ca2+. J Biol Chem 257 7495-7503. 

Due to the extraordinary toxicity of intact ribosome-inactivating toxins like ricin, abrin, and modeccin, purification and handling of these proteins must be done with extreme care. Even dust from crude seed powders or lyophilized proteins should be considered dangerous. During... 

Olsnes, S., and Pihl, A. (1976) Abrin, ricin, and their associated agglutinins. In The Specificity of Animal, Bacterial and Plant Toxins. Receptors and Recognition (P. Cuatrecasas, ed.), Series B, Vol. 1, pp. 129-173. Chapman Hall, London. 

Toxin A chains are isolated from ricin and abrin by reductive cleavage of the toxin, followed by separation of the chains These procedures are hazardous and should not be undertaken without the proper safeguards (4). 

Commercially obtained preparations of ricin A chain and abrin A chain may require further purification to eliminate traces of contaminating toxin B chains. The simplest procedure is to pass the A chain preparation over a column of Sepharose-linked asialofetuin, to which the B chains bind avidly (4,11)... 

Antibody-toxin conjugates made with ricin A chain, abrin A chain, gelomn, and momordin can be stored for at least 4 yr at -70°C without detectable loss of activity. The bond between the antibody and the RIP breaks down very slowly at 4°C in PBSE but, provided that care is taken to ensure the sterility of the solution, conjugates can be stored under these conditions for up to one year with little deterioration in quality. 

Fig. 1. Gel permeation chromatography of an antibody-toxin conjugate reaction mixture. The reaction mixture obtained following the conjugation of a mouse monoclonal antibody (50 mg) and [l25I]-labeled abrin A chain was chromatographed on a column of Sephacryl S-200 (SF), dimensions 80 cm x 2.6 cm (id). Fractions eluting from the column were monitored spectrophotometrically at 280 nm (—) to measure total protein, and by gamma counting (—) to measure the A chain in its free or conjugated form. The hatched area indicates a typical pooled conjugate preparation.

Fig. 2. SDS-PAGE of an antibody-toxin conjugate preparation. (A) Antibody (starting material). (B) Abrin A chain conjugate (pooled fractions shown in Fig. 1). Samples were prepared under nonreducing conditions and run on a 2—27% gradient polyacrylamide gel.

Similar toxic RIPs are found in other plants. Examples are trichosanthin, a type I toxin from the root tubers of Trichosanthes kirilowii (Cucurbitaceae), abrin, a type II toxin from the small brightly coloured red and black jequirity seeds (Abrus precatorius Leguminosae/Fabaceae), and viscumin, a type II toxin from the leaf and stems of mistletoe (Viscum album, Loranthaceae). 

The primary clinical targets of immunotoxins are tumors, based on the principle that the MAb will target the toxin to the tumor cells and the highly toxic moiety will then kill the cancer cells. Examples of toxins are ricin, diphtheria toxin and abrin, which are all glycoproteins. Their toxicity is based on their ability to block protein synthesis at the ribosomal protein assembly site. They are normally extremely toxic and not suitable for therapeutic purposes because they induce liver and vascular toxicity, even at low dose levels. 

Production, Stockpiling and Use of Chemical Weapons and on Their Destruction (CWC), and the international use of ricin or abrin as weapons is prohibited under the 1972 Convention on the Prohibition of the Development, Production and Stockpiling of Bacteriological (Biological) and Toxin Weapons and on Their Destruction (BTWC) Procedural Report and Rolling Text Ad Hoc Group 23rd session (April 23-May 11, 2001). 

The mechanisms of toxic action of abrin and ricin are similar. The B-chain attains cell recognition and binding function to facilitate toxin transport across the cell membrane, whereas the A-chain, once internalized by the cell, blocks protein synthesis by catalytically modifying the ribosomes. Both toxins ultimately kill target cells in animal or cell culture models by both necrosis and apoptosis. 

Numerous laboratory studies in mammals have demonstrated that ricin and abrin are highly toxic and potentially fatal to animals and humans. Major symptoms of both ricin and abrin poisoning are dependent on the route of exposure, the dose (or number of beans) received, or the content of toxin in the seed (or age of seed). Upon ingestion, toxicity is dependent on the degree of mastication if the bean was... 

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