Initiation of a transplantable fibrosarcoma by the synergism of two non-initiators, alpha-tocopherol and soya oil.

When, in the course of an ageing study, alpha-tocopherol (vitamin E), dissolved in soya oil, was given to 22 Balb/c mice once a week subcutaneously for 10 months, it caused the development of vigorously growing fibrosarcomata at the site of the injections in 17 (77.3%) of the animals. The tumors produced in this manner proved eminently transplantable into syngeneic Balb/c hosts, and have been serially transplanted every 3-4 weeks for over 3 years in such recipients, having reached their 44th transplantation cycle at the present time; upon transplantation, they now exhibit a 100% "take" incidence and proliferate extremely rapidly, growing from pin-head size to up to half the weight of a whole recipient mouse within 3 weeks. All fibrosarcomata showed marked mitotic activity, invasion of adjacent tissues and extensive necrotic areas, and they became more undifferentiated after the third transplantation cycle. Neither pure alpha-tocopherol alone nor soya oil alone produced any tumors when given subcutaneously once a week, for 10 months to groups of 22 Balb/c mice each. It is concluded that the two agents alpha-tocopherol and soya oil which proved non-carcinogenic when injected alone, developed a powerful carcinogenic effect when they acted on subcutaneous connective tissue simultaneously. The possible mechanisms of this phenomenon are discussed.