INHIBITORY EFFECTS OF ETHOXYQUIN, 4, 4'-DIAMINODIPHENYLMETHANE AND ACETAMINOPHEN ON RAT HEPATOCARCINOGENESIS

Abstract

Four antioxidant species, butylated hydroxyanisole (BHA), butylated hydroxy-toluene (BHT), ethoxyquin and α-tocopherol, and three other compounds, 4, 4'-diaminodiphenylmethane (DDPM), acetaminophen and glutathione, were tested for inhibitory effect on hepatocarcinogenesis in male F344 rats. Rats were initially given a single ip injection of diethylnitrosamine (200mg/kg body weight) and fed basal diet containing 0.02% 2-acetylaminofluorene from week 2 to week 8. Animals were subjected to partial hepatectomy at the end of week 3. From week 12 to week 36, they were given basal diet containing 2% BHA, 1% BHT, 0.8% ethoxyquin, 1% α-tocopherol, 0.1% DDPM, 1% acetaminophen, or 1% glutathione, then killed at week 40, 4 weeks after cessation of treatment with the test chemicals. The incidence of hepatocellular carcinoma (HCC) was significantly decreased in the groups given ethoxyquin or DDPM. Quantitative analysis of the number and area of HCC per unit liver area revealed a significant decrease in the area of HCC in the groups given ethoxyquin, DDPM or acetaminophen. The results suggest that ethoxyquin, DDPM and acetaminophen exerted an inhibitory effect on the development of HCC, while BHA, BHT, α-tocopherol and glutathione had no significant effect.