Initiating Activity of Aromatic Hydrocarbons in Two-Stage Carcinogenesis2

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Abstract
Compounds which are noncarcinogenic or weakly carcinogenic in most biological test systems have shown pronounced tumor-initiating activity on mouse skin. In these experiments, a single dose of the initiating agent was applied on mouse skin (ICR/Ha Swiss) followed by repeated application of phorbol myristate acetate for 1 year or longer. The classical “noncarcinogenic” aromatic hydrocarbon dibenz[a,c]anthracene, when tested in this manner, resulted in 25/70 mice with papillomas and 6/70 mice with squamous carcinoma of the skin after 1 year on test. When tested as an initiating agent, another weak carcinogen, benz[a]anthracene, also resulted in significant tumor yields: 10/20 mice with benign tumors. First tumors appeared at 51—74 days from the beginning of promoting treatment. The significance of these findings to tobacco carcinogenesis and other relevant aspects are discussed.

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