Depletion of the reduced glutathione level in the liver and production of the mutagens in the intestine in the mice inducing hepatoma by feeding on a high level dose of sorbic acid.
Mutagenicity was detected using Salmonella typhimurium TA98 in the acidic components of the intestinal contents of mice, in which a high incidence of hepatoma had been reported due to feeding on a diet containing 15% sorbic acid (Ishizawa et al., 1980). Furthermore, the glutathione level in the liver of the 15% sorbic acid group was decreased to 40% of the amount found in controls after a 3-month feeding period, and this low level was maintained for long periods (12 months) until the end of the experiments. There was also a close correlation between the extent of depletion of the hepato-glutathione level and the concentration of sorbic acid added to the diet. Consequently, the hepatoma which developed in mice fed a 15% sorbic acid diet was considered to be induced both by the depletion of the hepato-glutathione level over the long periods, and by the gradual production of various mutagens in the intestine which were absorbed and transferred to liver to be metabolically activated.
D000818:Animals; D001711:Biotransformation; D001835:Body Weight; D005231:Fatty Acids, Unsaturated / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008297:Male; D051379:Mice; D009154:Mutation / Q000187:drug effects; D009929:Organ Size; D010084:Oxidation-Reduction; D013011:Sorbic Acid / Q000633:toxicity*
D005231:Fatty Acids, Unsaturated; D005978:Glutathione; D013011:Sorbic Acid