Abstract
The effects of 3-O-dodecylcarbomethylascorbic acid (3-O-DAsA), 3-O-ethylascorbic acid (3-O-EAsA) and 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ) on 2-amino-6-methyldipyrido[1,2-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 mg 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.