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Four water-soluble carcinogens were injected at the same site subcutaneously into rats, mice or guinea-pigs, twice weekly for 5-8 weeks in order to study the evolution of the early tissue reaction. MNU was injected into rats as 0·1 ml. of 0·5% solution, and into mice as 0·1 ml. of 0·05% solution. NQO was administered to rats (0·1 or 0·2 ml. of 0·25 or 0·1%) mice (0·1 of 0·05%) and guinea-pigs (0·5 of 0·1%). Propane sultone and BEI were administered to rats only, the former as 0·1 ml. of 3% and the latter as 0·5 ml. of 2·0% solution.The principal features of the tissue reaction produced by each of the four compounds in rats were similar and consisted of destruction of subcutaneous tissue, deposition of fibrin and "fibrinoid", an abnormal pattern of fibroblastic proliferation with cytomegaly of some fibroblasts and deposition of mucopolysaccharide but little collagen formation. Moreover, the appearance of fibroblastic proliferation was delayed from the normal 2-5 days to 14-16 days.These features are consistent with the known early effects of carcinogens on proliferating target tissues, and differ considerably from those found in the early reactive lesions to repeated injection of solutions of substances possessing physical properties such as surface activity or hypertonicity, or which precipitate at the injection site.

Early Reactions of the Subcutaneous Tissue to Repeated Injections of Carcinogens in Aqueous Solutions