Effect of butylated hydroxyanisole on in vitro and in vivo nitrosation of dibutylamine

Biological actions of 4 commonly used synthetic antioxidants--butylated hydroxyanisole, butylated hydroxytoluene, ethoxyquin and propyl gallate--on the molecular, cellular and organ level are complied. Such actions may be divided into modulation of growth, macromolecule synthesis and differentiation, modulation of immune response, interference with oxygen activation and miscellaneous. Moreover, an overview of beneficial and adverse interactions of these antioxidants with exogenous noxae is given. Beneficial interactions include radioprotection, protection against acute toxicity of chemicals, antimutagenic activity and antitumorigenic action. Possible mechanisms of the antitumorigenic action of antioxidants are discussed. This discussion is centered around antioxidant properties which may contribute to a modulation of initiation-related events, especially their ability to interfere with carcinogen metabolism. The beneficial interactions of antioxidants with physical and chemical noxae are contrasted to those leading to unfavorable effects. These include radiosensitization, increased toxicity of other chemicals, increased mutagen activity and increased tumor yield from chemical carcinogens. At present, the latter one can most adequately be characterized as tumor promotion at least in the case of butylated hydroxytoluene. It is concluded that current information is insufficient to promote expectations as to the use of antioxidants in the prevention of human cancer.

Caffeic acid and ferulic acid, which are naturally occurring phenols present in a wide variety of plants, were examined for their ability to react with nitrite in vitro and to inhibit nitrosamine formation in vivo. Their activities were compared with other phenols (butylated hydroxyanisole and Trolox) and with a non-phenolic polyhydroxylated compound, glycerol guaiacolate. In simulated gastric fluid, caffeic acid and ferulic acid reacted rapidly and completely with an equimolar quantity of sodium nitrite. In rats receiving aminopyrine and nitrite, caffeic acid and ferulic acid blocked the elevation of serum N-nitrosodimethylamine (NDMA) levels and the serum glutamic pyruvic transaminase levels associated with hepatotoxicity. Neither phenol had any effect on serum levels of NDMA in rats treated with NDMA. In both the in vitro (reaction with nitrite) and in vivo (inhibition of hepatotoxicity) systems, caffeic acid was more effective than ferulic acid. Butylated hydroxyanisole and Trolox were partially effective, and glycerol guaiacolate was inactive. The results of this study suggest that dietary caffeic acid and ferulic acid may play a role in the body's defense against carcinogenesis by inhibiting the formation of N-nitroso compounds.