Modifying effects of S-
methyl methanethiosulfonate (
MMTS) on
diethylnitrosamine (DEN)-initiated and
phenobarbital (PB)-promoted hepatocarcinogenesis were examined in rats. Five-week-old male F344 rats were divided into 8 groups. After a week, groups 1-5 were given DEN (100 mg/kg
body weight, i.p.) once a week for 3 weeks, whereas groups 6-8 received vehicle treatment. Group 2 was given 100 ppm
MMTS containing diet in the initiation phase. From 4 weeks after the start of experiment, groups 3 and 5 were fed
MMTS, and groups 1-3 and 7 received
drinking water containing 500 ppm PB. Group 6 was given
MMTS diet alone throughout the experiment (24 weeks). The incidences of
hepatocellular adenoma and total liver
tumors were significantly smaller in group 3 than those of group 1. The average numbers of
hepatocellular adenoma,
carcinoma and total
tumors in group 3 were significantly smaller than in group 1.
Glutathione S-transferase placental form-positive foci were also significantly decreased by
MMTS treatment in the promotion phase.
MMTS treatment in the initiation or promotion phase reduced
ornithine decarboxylase activity in the liver of rats given DEN. The
antioxidant activity against lipid peroxidation of
MMTS was confirmed in tests with rabbit erythrocyte membrane ghosts or rat hepatocytes. These results suggest that
MMTS is a promising chemopreventive agent for liver
neoplasia when concurrently administered with PB.