Tests of chemical substances for mutagenic action.

The discovery in 1941 (Auerbach and Robson, first published in 1946) that mustard gas (β-β′-dichloro-diethyl-sulphide), (ClCH2.CH2)2S, is comparable to X-rays in its capacity to produce mutations and chromosome rearrangements naturally raised the question as to what special properties of mustard gas enable it to act in this manner. There are indications (Auerbach and Robson, 1947) that the mutagenic effects of mustard gas are due to a direct action on the chromosomes, and not to an indirect one via the cytoplasm. This suggests that a selective and specific chemical reaction occurs between mustard gas and the genie material. It appeared possible that a systematic survey of substances chemically related to mustard gas might reveal a chemical group or structural arrangement responsible for the mutagenic action. This in its turn might also throw some light on the other component of the reaction, the gene or chromosome, and on the process of mutation itself. The substances, to be tested were, with one exception, chosen on account of their chemical and pharmacological similarity to mustard gas. They were: (1) N-methyl di-(2-chloroethyl) amine, CH3.N(CH2.CH2Cl)2, one of the so-called nitrogen mustards. This is a liquid with strong vesicant action. It decomposes fairly rapidly in water. Its hydrochloride is a solid, soluble in water and forming a stable solution. This solution proved useful in certain tests in which it was convenient to apply a mutagenic substance in aqueous solution.