Mode of Production of Chromosome Abnormalities by the Nitrogen Mustards The Possible Role of Cross-Linking

A Comparative Study of the Activity of Some Cytostatic Agents on a Biological Test ‘in vivo’

“…As for E-39 activity, it seems likely that two different anti proliferative pathways are present: the antimitotic action of hydroquinoncs and the well known effect of aethylene-imino radicals on nuclei in pre-mitotic stage (as for all nitrogen mustard derivatives (8). This twofold action could justify the greater activity and toxi city of this substance, especially with regard to methyl-bis-chloroaethyl-amine.…”

Cytotoxic Agents: Iv, the Carcinogenic Actions of Some Monofunctional Ethyleneimine Derivatives

“…358), while molecules containing two or three such reactive groups may be presumed to combine at more than one nucleophilic centre. It was this possibility with the nitrogen mustards in particular that led Goldacre, Loveless, and Ross (1949) to suggest " crosslinkage" as the mechanism by which these agents exert their characteristic action on dividing cells. In their hypothesis nucleophilic centres in sister chromatids were regarded as the respective sites of attachment of each polyfunctional molecule of the agent.…”

Miscellaneous Chemical Carcinogens: Chemical Constitution and Carcinogenic Activity

“…An hypothesis (Goldacre, Loveless and Ross, 1949) that the action might be associated with a cross-linkage reaction directed attention to known cross-linking agents for textile fibres; but subsequent work has shown that some mono-functional alkylating agents have carcinogenic activity.…”

“…Following the cross-linking hypothesis of Goldacre, Loveless and Ross (1949) bis-epoxides were found to possess the tumour-inhibiting activity and to produce the chromosome abnormalities characteristic of the mustards. Only two compounds of this type seem to have been tested for carcinogenic activity.…”