The synthetic monocyclic phenolics (MPs),
acetaminophen (
APAP),
butylated hydroxyanisole (
BHA), and
butylated hydroxytoluene (
BHT) are antimutagenic or anticarcinogenic against a diversity of chemical
carcinogens affecting a variety of tissues in experimental animals. In studies in this laboratory of the anticarcinogenicity of MPs, the focus has been on delineating efficacy at low levels of MPs that do not elicit adaptive or toxic responses. To accomplish this, we are studying anticarcinogenicity against the neoplastic initiating activity of lower doses of
carcinogens than have previously been studied and which are closer to human environmental exposures. In these studies, we have investigated anticarcinogenicity of
BHT against
liver cancer in rats induced by either
2-acetylaminofluorene (AAF) or
aflatoxin B1 (AFB1) and anticarcinogenicity of
APAP against
colon cancer induced in rats by
3,2'-dimethyl-4-aminobiphenyl (DMAB).
BHA and
BHT at 100-125 ppm in the diet inhibited the initiation phase of AAF and AFB1 hepatocarcinogenesis and therefore may act intracellularly to block effects of the
carcinogen. Likewise, with
APAP in colon anticarcinogenicity, at 1000 ppm it reduced
DNA binding and exerted a cytoprotective effect against DMAB. Thus,
APAP also shows evidence of producing a blocking effect. We conclude that these MPs appear to be anticarcinogenic through a mechanism different from that of most other chemopreventive agents, possibly involving interception of the reactive chemical species of the
carcinogen. Accordingly, they have promise as
cancer prophylactics, including in combination with agents operating through other mechanisms.