Download Advances in Cancer Research [Vol II] by J. Greenstein, et al., PDF

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I n its simplest form direct action can only produce a change if the ionization occurs within the sensitive area of an organism or a macromolecule. The area of the “target” may, however, be considerably extended if the reaction of the ejected electron is considered. Thus after a direct hit of a macromolecule (M) the following series of reactions may occur in a living system (Burton, 1952). , not within the target) the HOz radical produced may diffuse to the target site and react there. Considerations such as these may resolve the controversy (cf.

1950, 1951a,b,c) suggest that the cytotoxic alkylating agents polymerize in situ to give a macromolecule containing reactive groups. The necessity for two functional groups, according to this hypothesis, arises from the fact that one brings about the joining up of THE REACTIONS OF CARCINOQENS WITH MACROMOLECULES 21 the molecules into a polymer and the second group provides the reactive centers in the polymer. The types of structure postulated for bis-epoxides, bis-ethyleneimines and nitrogen mustards are shown in Figs.

0 CH~--CH-CHz--CH-CHx \d \d ’ Ratio of Salmine Combined with Nucleic Acid before and after Reaction X x-c ! 2 pound, namely that the reactive groups within the same moleculeshould be placed in such a way that they can form a ring (see p. lo), follows directly if reaction with adjacent groups is required. I t is suggested that the repulsion between charged groups is sufficient to maintain the molecule highly extended even when isolated phosphate groups have been esterified by reaction with a monofunctional compound, but that, after blocking two adjacent anions with a bifunctional compound, the distance separsting charged groups is too great for electrostatic effects to keep the molecule rigid a t this point.

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