Further Immunological Studies of Chemical Carcinogenesis2

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Abstract
The effect of the carcinogenic hydrocarbon 3-methylcholanthrene (MCA) on the immune status of the exposed host was studied at the cellular level. A hemolytic agar-plaque technique, measuring single plaque-forming spleen cells (PFC) toward the test antigen, sheep red blood cells (SRBC), was used. 1) Kinetic studies of PFC numbers following a single exposure to MCA showed that the previously observed, long-lasting immunodepression, which corresponded to the latency period before antigenic MCA-induced sarcomas appeared, was real and not due only to a delay of the immune response. 2) An early stage in the process leading to PFC, possibly related to the uptake of the antigen, was specifically sensitive to the effect of MCA. Once the process was started, MCA had a much smaller effect. 3) Dose-effect relationship studies of MCA dose versus PFC depression showed that the PFC number dropped sharply when the dose was increased from 0.1–1.0 mg MCA. Further increase up to 5.0 mg had little effect. 4) Repeated exposure to small doses of the carcinogen led to a cumulative immunodepressive effect comparable to the total dose. 5) Cutaneous application of MCA and of croton oil depressed the PFC. Combined with earlier findings, the results suggest a possible correlation between immunodepression and antigenicity of the tumors arising after exposure.