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The Synergistic Action of Mixtures of Certain Hepatic Carcinogens^*

( McArdle Memorial Laboratory, Medical School, University of Wisconsin, Madison 6, Wis.)

1. When 2-acetylaminofluorene and 3'-methyl-4-dimethylaminoazobenzene were fed simultaneously in a grain diet to male rats, the incidence of hepatic tumors was greater than the sum of the tumor incidences obtained when the carcinogens were fed singly. No synergistic effect on liver tumor induction was observed when 3'-methyl-4-dimethylaminoazobenzene and 3-acetylaminodibenzothiophene or 4'-methyl-4-dimethylaminoazobenzene and 2-acetylaminofluorene were fed together.

2. The incidence of tumors arising from the ear duct was greater in rats fed both 3'-methyl-4-dimethylaminoazobenzene and 3-acetylaminodibenzothiophene than in animals fed only the latter compound. 3'-Methyl-4-dimethylaminoazobenzene did not augment the induction of ear duct tumors by 2-acetylaminofluorene.

3. The simultaneous administration of 0.032 per cent of 4'-methyl-4-dimethylaminoazobenzene and 0.030 per cent of 4-dimethylaminoazobenzene was a more effective carcinogenic stimulus for the liver of male rats than either 0.030 per cent of 4-dimethylaminoazobenzene or 0.064 per cent of 4'-methyl-4-dimethylaminoazobenzene alone; it was a less effective dose than 0.060 per cent of 4-dimethylaminoazobenzene.

4. 2-Acetylaminofluorene and 3-acetylaminodibenzothiophene also induced tumors in the small intestinal epithelium of 10–35 per cent of the rats fed these compounds.

^* This work was supported in part by grants from the National Cancer Institute, Public Health Service, and the American Cancer Society upon recommendation by the National Research Council.

Received 9/25/51.