Strong Inhibition of 2‐Amino‐6‐methyldipyrido[l,2‐a:3′,2′‐d]imidazole‐induced Mutagenesis and Hepatocarcinogenesis by 1‐O‐Hexyl‐2,3,5‐trimethylhydroquinone

The effects of 3‐O‐dodecylcarbomethylascorbic acid (3‐O‐DAsA), 3‐O‐ethylascorbic acid (3‐O‐EAsA) and 1‐O‐hexy1‐2,3,5‐trimethylhydroquinone (HTHQ) on 2‐amino‐6‐methyldipyrido[l,2‐a:3′,2′‐d]‐imidazole (Glu‐P‐1)‐induced mutagenesis and hepatocarcinogenesis were examined. In a Salmonella assay, addition of 2.5 to 20.0 rag of HTHQ to Salmonella TA 98 in the presence of S‐9 mixture dose‐dependently inhibited Glu‐P‐1‐induced mutagenesis. The highest dose showed a 99% reduction in revertants. 3‐O‐DAsA and 3‐O‐EAsA were without effect. In an animal study using the medium‐term bioassay system for the detection of hepatocarcinogens or hepatopromoters in F344 male rats, treatment with Glu‐P‐1 alone was associated with a significant increase in the number and area of GST‐P‐positive foci (47.5±8.9 and 11.1±4.7, respectively). Combined treatment with 1.0% HTHQ significantly reduced the number and area of GST‐P‐positive foci (to 8.1±2.1 and 0.6±0.2) while 3‐O‐DASA exerted marginal inhibition and 3‐O‐EAsA had no effect. On the other hand, all three of these compounds slightly enhanced the numbers and areas of foci when given alone. The results indicate that HTHQ is a potent chemopreventer of Glu‐P‐1‐induced hepatocarcinogenesis.