Change in the gene expression of the N-methyl-D-aspartate receptor 2C subunit by dietary β-naphthoflavone, indole-3-carbinol, or acetaminophen in the rat liver.

We have previously demonstrated super-induced expression of the Grin2c gene encoding the N-methyl-D-aspartate receptor 2C subunit during the process of liver enlargement induced by phenobarbital, clofibrate, piperonyl butoxide, or lead nitrate. In the present study, hepatic Grin2c gene expression levels were assessed by real-time RT-PCR in male F344 rats fed for 3 days, 4 weeks, and 13 weeks a diet containing either β-naphthoflavone (BNF) (5,000 ppm), indole-3-carbinol (I3C) (2,000 ppm), or acetaminophen (AA) (12,500 ppm until the first 14 days; 10,000 ppm from 15 days on), each of which is capable of inducing hepatocellular hypertrophy. Especially, either the 4-week or the 13-week treatment with each chemical, except for BNF, resulted in a drastic increase in the expression level of the Grin2c gene. DNA microarray analysis using RNAs of 13-week-treated rats showed that in the I3C- and AA-treated rats, the fold-increase rates of the Grin2c gene ranked second and first, respectively, among the genes analyzed. Histopathological analyses indicated that the slight hepatocellular hypertrophy in the periportal area and the hepatocellular necrosis in a portion of the centrilobular area developed in the BNF-treated and AA-treated rats, respectively. In addition, relative liver weight was significantly higher in the rats treated with BNF and I3C than in the control rats. The present findings suggest the possibility that the induction of Grin2c gene expression is not necessarily dependent on only the development of liver enlargement, although the significance of this induction remains unclear.