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Carcinogenicity of Multiple Chemicals Simultaneously Administered^*

( Department of Pathology, University of Chicago, Chicago 37, Ill.)

Aromatic polycyclic hydrocarbons in various combinations were tested for carcinogenic activity in the subcutaneous tissues of C57BL mice. Three strong carcinogens tested with a medium-strength chemical (1,2-benzanthracene) caused, variously, summation effects (with 20-methylcholanthrene) or no effect (1,2,5,6-dibenzanthracene; 3,4-benzpyrene). A strong carcinogen (1,2,5,6-dibenzanthracene) did not summate effects with a weak agent (chrysene). Chemically related but noncarcinogenic compounds (anthracene, phenanthrene) added to a strong carcinogen (1,2,5,6-dibenzanthracene) did not affect the tumor yield; they were not co-carcinogenic. Doubling the amount of each of two strong carcinogens increased the tumor yield over either alone. As the dose of a medium strength carcinogen (1,2-benzanthracene) was reduced, the tumor yield decreased. However, when these amounts of the chemical were tested with a constant quantity of a strong carcinogen (1,2,5,6-dibenzanthracene), no similar decrease followed but rather a summation of carcinogenic effects at the lower doses. Chrysene and 1,2-benzanthracene were again found to be carcinogenic, and anthracene and phenanthrene to be inactive. With the agents and dosages here used, no striking effects were observed on carcinogenic activity except when the dosage of one agent was greatly reduced (Experiment 8); here a summation effect was obtained.

^* This study was aided by a grant from the American Cancer Society, on recommendation of the Committee on Growth of the National Research Council.

Received 6/11/55.