Correlation of antimutagenic activity and suppression of CYP1A with the lipophilicity of alkyl gallates and other phenolic compounds.
Alkyl gallates are widely used as food antioxidants. Methyl, ethyl, propyl, lauryl, and cetyl gallates showed antimutagenicity to activated 2-aminoanthracene (2AA)-induced SOS responses in Salmonella typhimurium TA1535/pSK1002. They also exhibited a suppressive effect on 3-methylcholanthrene (3-MC)-induced cytochrome P450 1A (CYP1A) in human hepatoma HepG2 cells, as indexed by the 7-ethoxyresorufin-O-deethylase (EROD) activity, and on CYP1A protein level. Both antimutagenicity and suppression of CYP1A appeared to be dependent on alkyl chain lengths, which suggested lipophilicity dependence. Based on those results, we investigated 26 other phenolic compounds for their lipophilicity, antimutagenicity and inhibition of EROD activity. The lipophilicity correlated well with the inhibition of EROD activity (r=0.78), and the inhibition of EROD activity correlated with the antimutagenicity of those compounds (r=0.71). The results suggest that the lipophilicity of the phenolic compounds may be an important factor in their ability to inhibit EROD activity.
Feng
Qing
Q
Laboratory of Food and Biodynamics, Graduate School of Bioagricultural Sciences, Nagoya University, 464-8601, Nagoya, Japan.
Kumagai
Takeshi
T
Nakamura
Yoshimasa
Y
Uchida
Koji
K
Osawa
Toshihiko
T
D000873:Anthracenes / Q000494:pharmacology; D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics* / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics* / Q000378:metabolism; D005707:Gallic Acid / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D008956:Models, Chemical; D009153:Mutagens; D019800:Phenol; D010636:Phenols / Q000494:pharmacology; D012486:Salmonella typhimurium / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000873:Anthracenes; D000975:Antioxidants; D009153:Mutagens; D010636:Phenols; D019800:Phenol; D005707:Gallic Acid; C006593:2-anthramine; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2