By J. Greenstein, et al.,
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A 3 X lo-* mole of reagent were applied per 1 g. of wool suspended in 26 ml. Flask shaken for 72 houre at 4OOC. 6 From Van Slyke determination. d From titration data. From quantity of dinitrophenyllysine formed on treatment with dinitrotluorobenzene. I Titration data could not be evaluated since introduced basic groups interfere. Reaction between nitrogen mustards and protein carboxyl groups cannot readily be detected from changes in acid combination since the titration of ‘the mustard amine to its salt and the back titration of the carboxyl ion with acid occur in the same pH range.
As the animal gets older, there is evidence that the rate of breakdown of proteins becomes less (cf. , 1951), and it is possible that crosslinked structures may then accumulate. Alternatively with decreased rate of metabolic turnover there may be time for the crosslinking process to proceed to such an extent that the product can no longer be broken down in the body. In this connection attention may be drawn to the production of cancer by the introduction of inert films (see p. 65) since their effect might be comparable t o the accumulation of a highly insoluble metabolic product.
More detailed investigation (Butler and James, 1951) of the physical properties of mustard-treated DNA has definitely established that the initial reaction which produces such pronounced physical changes is not due to depolymerization and is probably brought about in one of the ways discussed above. There are indications (Butler, Gilbert, and James, 1952), however, that the spontaneous degradation by hydrolysis which is known to occur in solution (cf. , 1918) takes place somewhat more readily after reaction with the mustards.