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2617. Alkylation by propylene oxide
MISCELLANEOUS
DIRECT
ADDITIVES
1143
inhibitor, because it indicates that this ability is accounted for in part by reaction of DPC with nucleic acid components, it may also suggest potential applications for the compound in determinations of nucleic acid structure. 2617. Alkylation
by propylene oxide
Lawley, P. D. 8c Jarman, M. (1972). Alkylation by propylene oxide of deoxyribonucleic acid, adenine, guanosine and deoxyguanylic acid. Biochenl. J. 126, 893. Propylene oxide appears in industry as a by-product in a number of processes, but data on the toxicological properties of this reactive chemical are not extensive. It has also been used as a food fumigant (Cited in F.C.T. 1966 4,456 & 607; ibid 1967, 5, 425), although it is less popular in this respect than ethylene oxide. An alkylating agent, it is known to be mutagenic for Drosophila, but its possible effects on chromosome structure in animals do not appear to have been investigated in detail. The main in uiuo target for alkylation by this epoxide would be expected to be DNA, and the present work was carried out to investigate the possible reaction between propylene oxide and this nucleic acid, the limited earlier studies in this connexion having produced somewhat inconclusive results. The oxide was shown to react to some extent with DNA in aqueous buffer solution at roughly neutral pH to yield two main products, identified by their ultraviolet absorption spectra as 7-(2-hydroxypropyl)guanine and 3-(2-hydroxypropyl)adenine after hydrolysis of the alkylated DNA. The same products were separated and isolated after reaction of propylene oxide with guanosine and adenine, respectively. The latter reaction, in acetic acid, closely resembled that between dimethyl sulphate and adenine in neutral solution, the degree of reactivity of the alkylated positions in adenine being in both cases N-3> N-l > N-9. In the case of the propylene oxide/guanosine reaction in neutral solution, alkylation was apparently confined to the N-7 position on the base. Mass spectrometric analysis of the major alkylation products led to the suggestion that propylene oxide reacts largely through operation of a bimolecular S,2 alkylation mechanism. The possibility of S,l-type reactivity could not be completely eliminated, however, in view of the limitations of the techniques used.
MISCELLANEOUS
DIRECT
ADDITIVES
2618. Evaluation of FPC Newberne, P. M., Glaser, O., Friedman, L. & Stillings, B. (1973). Safety evaluation protein concentrate over five generations of rats. Toxic. appl. Pharmac. 24, 133.
of fish
Fish meal has been used in animal feeds for a number of years as a valuable source of high-quality protein, and the needs of an increasing world population have led to the development of a fish-protein concentrate (FPC) for human consumption. This greyish, tasteless and odourless powder can be obtained from species which would normally have little economic value, and 10 g FPC has been estimated to supply the minimum daily animalprotein requirements of the average adult. Thus the present study was carried out to demonstrate the safety and wholesomeness of FPC prepared from red hake.
DIRECT
ADDITIVES
1143
inhibitor, because it indicates that this ability is accounted for in part by reaction of DPC with nucleic acid components, it may also suggest potential applications for the compound in determinations of nucleic acid structure. 2617. Alkylation
by propylene oxide
Lawley, P. D. 8c Jarman, M. (1972). Alkylation by propylene oxide of deoxyribonucleic acid, adenine, guanosine and deoxyguanylic acid. Biochenl. J. 126, 893. Propylene oxide appears in industry as a by-product in a number of processes, but data on the toxicological properties of this reactive chemical are not extensive. It has also been used as a food fumigant (Cited in F.C.T. 1966 4,456 & 607; ibid 1967, 5, 425), although it is less popular in this respect than ethylene oxide. An alkylating agent, it is known to be mutagenic for Drosophila, but its possible effects on chromosome structure in animals do not appear to have been investigated in detail. The main in uiuo target for alkylation by this epoxide would be expected to be DNA, and the present work was carried out to investigate the possible reaction between propylene oxide and this nucleic acid, the limited earlier studies in this connexion having produced somewhat inconclusive results. The oxide was shown to react to some extent with DNA in aqueous buffer solution at roughly neutral pH to yield two main products, identified by their ultraviolet absorption spectra as 7-(2-hydroxypropyl)guanine and 3-(2-hydroxypropyl)adenine after hydrolysis of the alkylated DNA. The same products were separated and isolated after reaction of propylene oxide with guanosine and adenine, respectively. The latter reaction, in acetic acid, closely resembled that between dimethyl sulphate and adenine in neutral solution, the degree of reactivity of the alkylated positions in adenine being in both cases N-3> N-l > N-9. In the case of the propylene oxide/guanosine reaction in neutral solution, alkylation was apparently confined to the N-7 position on the base. Mass spectrometric analysis of the major alkylation products led to the suggestion that propylene oxide reacts largely through operation of a bimolecular S,2 alkylation mechanism. The possibility of S,l-type reactivity could not be completely eliminated, however, in view of the limitations of the techniques used.
MISCELLANEOUS
DIRECT
ADDITIVES
2618. Evaluation of FPC Newberne, P. M., Glaser, O., Friedman, L. & Stillings, B. (1973). Safety evaluation protein concentrate over five generations of rats. Toxic. appl. Pharmac. 24, 133.
of fish
Fish meal has been used in animal feeds for a number of years as a valuable source of high-quality protein, and the needs of an increasing world population have led to the development of a fish-protein concentrate (FPC) for human consumption. This greyish, tasteless and odourless powder can be obtained from species which would normally have little economic value, and 10 g FPC has been estimated to supply the minimum daily animalprotein requirements of the average adult. Thus the present study was carried out to demonstrate the safety and wholesomeness of FPC prepared from red hake.