Occurrence of pulmonary tumors in strain A mice following total-body X-radiation and injection of nitrogen mustard.

One of the sources of evidence for the somatic mutation hypothesis of cancer is in studies of cor relation between mutagenic and carcinogenic ca pacities of physical and chemical agents. Tests in this laboratory have suggested a positive correla tion within the limits of three mustard compounds. Both the nitrogen mustard, methylbis (2-chloroethyl)amine hydrochloride, and sulfur mustard, bis(2-chloroethyl) sulfide, were shown to be strong carcinogens in the induction of pulmonary tumors when injected intravenously into strain A mice (9, 10). Both had been demonstrated to be strong mutagens when tested on Drosophila and micro organisms,1 and recently Falconer, Slizynski, and Auerbach (6) have reported genetic changes in the progeny of mice treated with nitrogen mustard. On the other hand, mustard oil, allyl iso-thiocyanate, that Auerbach and Robson (3) found to be a weak mutagen when tested on Drosophila, did not significantly increase the occurrence of pulmonary tumors in strain A mice. Such studies are logically extended to the ob servation of the effect of combining agents which individually have carcinogenic effects and for which additive mutagenic effects have been dem onstrated. Radiation and the mustards comprise such combinations. The carcinogenic action of radiation has long been established, and, in the work of Lorenz et al. (21), an increase in the occurrence of lung tumors in strain A mice was observed following exposure to chronic gamma radiation, and later such an increase was also ob served following fractionated acute x-radiation (18). Aside from the demonstration of an increase in pulmonary tumors in strain A mice injected with nitrogen and sulfur mustard (9, 10), carcin* With the technical assistance of Wayne D. Levillain.