Cocarcinogenic and tumor-promoting agents in tobacco carcinogenesis.

A series of 21 tobacco smoke components and related compounds werere applied to mouse skin (50 female ICR/Ha Swiss mice/group) three times weekly with a low dose (5 mug/application) of benzo[a]pyrene (B[a]P). The test compounds were of five classes: aliphatic hydrocarbons, aromatic hydrocarbons, phenols, and long-chain acids and alcohols. The following compounds enhanced remarkably the carcinogenicity of B[a]P: catechol, pyrogallol, decane, undecane, pyrene, benzo[e]pyrene, and fluoranthene. The following compounds inhibited B[a]P carcinogenicity completely: esculin, quercetin, squalene, and oleic acid. Phenol, eugenol, resorcinol, hydroquinone, hexadecane, and limonene partially inhibited B[a]P carcinogenicity. Six of the 21 compounds were also tested as tumor promoters im two-stage carcinogenesis. No direct correlation existed between tumor-promoting activity and cocarcinogenic activity. The cocarcinogens pyrogallol and catechol did not show tumor-promoting activity. Decane, tetradecane, anthralin, and phorbol myristate acetate showed both types of activity. Structure-activity relationships and possible modes of action were described.