Chromosome Alteration and Tumour Inhibition by Nitrogen Mustards: the Hypothesis of Cross-linking Alkylation

Abstract

THE hypothesis has been advanced that the ‘radiomimetic’ activity of nitrogen mustards depends on the presence of two reactive groups in the mustard molecule. It has been further suggested that chromosome bridging and breakage, which result from treatment of proliferating cells with mustards, are a direct consequence of interchromatid cross-linkage by single polyalkylating molecules^1,2. Such a mechanism of chromosomal damage could be considered as a plausible explanation of the effective actions of nitrogen mustards and certain other polyfunctional molecules, such as polyethylenimines and diepoxides, against mammalian tumours. However, recent studies of a number of monofunctional compounds related in structure to nitrogen mustards and diepoxides raise some questions concerning the validity of these generalizations.