cinnamyl-anthranilate and Body-Weight

The effects of cinnamyl anthranilate (CA) have been compared in female B6C3F1 mice and female F344 rats fed diets containing 0-3.0% CA for periods of 1, 4, and 13 weeks. In the mouse, treatment with CA at all time points produced a marked dose-dependent increase in relative liver weight and hepatic peroxisome proliferation as demonstrated by the induction of peroxisomal (cyanide-insensitive palmitoyl-CoA oxidation) and microsomal (lauric acid 12-hydroxylase) fatty acid oxidizing enzyme activities. CA produced only small increases in relative liver weight and palmitoyl-CoA oxidation in the rat and did not induce lauric acid 12-hydroxylase activity. Replicative DNA synthesis was studied by implanting osmotic pumps containing 5-bromo-2'-deoxyuridine during Study Weeks 0-1, 3-4, and 12-13. After 1 week of CA treatment, labeling index values were increased in rat and to a greater extent in mouse hepatocytes. While CA treatment for 4 and 13 weeks did not increase hepatocyte-labeling index values in the rat, a sustained stimulation of replicative DNA synthesis was observed at some dietary levels in the mouse. These results demonstrate a marked species difference between the hepatic effects of CA in female B6C3F1 mice and female F344 rats. While CA is a potent peroxisome proliferator in the mouse, it is only a very weak agent in the rat. The formation of liver tumors in long-term studies, at high doses of CA, appears to be attributable to a sustained stimulation of both peroxisome proliferation and cell replication in mouse hepatocytes.

Topics: Animals; Body Weight; Cell Division; Cytochrome P-450 CYP4A; Cytochrome P-450 Enzyme System; DNA Replication; Dose-Response Relationship, Drug; Eating; Enzyme Induction; Female; Flavoring Agents; Liver; Mice; Microbodies; Mixed Function Oxygenases; Organ Size; ortho-Aminobenzoates; Rats; Rats, Inbred F344; Species Specificity