Management of an Artery-Graft Bank

Rains, A. J. Harding; Crawford, Neil R.; Sharpe, Sophie; Shrewsbury, J. F. D.; Barson, G.J.

doi:10.1016/s0140-6736(56)92264-4

Cited by 25 publications

(2 citation statements)

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“…It has many possible uses as an organic synthetic agent, and has been recommended for sterilising plasma (Hartmann, LoGrippo and Kelly, 1954) and arterial grafts (Rains et al, 1956) and as a toxoiding agent in place of formalin (Orlans and Jones, 1958). It is therefore of importance that ,-propiolactone, besides being a vesicant, is also a mutagenic agent (Smith and Srb, 1951), has been found to cause sarcomas after injection in arachis oil into rats (Walpole et al, 1954) and gives rise to papillomas and squamous cell carcinomas when applied in acetone solution to mouse skin (Roe and Glendenning, 1956).…”

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Experiments on the Carcinogenicity and Reactivity of β-propiolactone

Searle¹

1961

Br J Cancer

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fi-PROPIOLACTONE (3-hydroxypropionic acid lactone, O.CH2.CH2C: O) is a highly reactive compound of simple structure which is now available in quantity. It has many possible uses as an organic synthetic agent, and has been recommended for sterilising plasma (Hartmann, LoGrippo and Kelly, 1954) and arterial grafts (Rains et al., 1956) and as a toxoiding agent in place of formalin (Orlans and Jones, 1958). It is therefore of importance that ,-propiolactone, besides being a vesicant, is also a mutagenic agent (Smith and Srb, 1951), has been found to cause sarcomas after injection in arachis oil into rats (Walpole et al., 1954) and gives rise to papillomas and squamous cell carcinomas when applied in acetone solution to mouse skin (Roe and Glendenning, 1956). fi-Propiolactone is thus suspect as a carcinogen to man, and Roe and Salaman (1958) have questioned the advisability of using it for arterial graft sterilisation.Apart from such practical considerations, it is of considerable theoretical interest that relatively simple compounds such as /-propiolactone and various ethyleneimines should have carcinogenic activity. It is possible that studying the biological reactivity of these substances, which Walpole et al. (1954) suggested may act as carcinogens per se, could give more useful information about the carcinogenic process than has hitherto been obtained from work on the aromatic hydrocarbon carcinogens. Dickens and Jones (1961) have now shown that a range of other lactones can induce sarcomas when repeatedly injected into rats. Structural features of the active compounds are either a highly strained four-membered ring as in fipropiolactone and penicillin G, or a five-membered ring with double bonds in the 2-and/or 4-positions, as in patulin and penicillic acid. A number of these compounds have also antibiotic and growth inhibitory activity, and are inactivated by cysteine.Among other reactions of ,8-propiolactone those with biological sulphydryl groups are of particular interest. Searle (1961) investigated the effects of fl-propiolactone on the sulphydryl and disulphide groups of egg and serum albumins by polarography of the denatured protein solutions at intervals after adding the lactone. It was found that fl-propiolactone caused immediate destruction of polarographically active groups in the albumins, but that these effects were reversible when the solutions were warmed or allowed to stand at room temperature.This could indicate that the main product from the reaction of f-propiolactone with cysteine residues in the protein has a hydrolysable thioester grouping. In

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