Catechin inhibition of mutagenesis and alteration of DNA binding of 2-acetyl-aminofluorene in rat hepatocytes.
Bioflavonoids are naturally occurring plant products that have demonstrated inhibitory effects on chemically induced carcinogenesis or mutagenesis. The chemoprotective effects are either direct scavenging of reactive molecules or indirect effects, such as enzyme activity alteration. Exposure of cultures of isolated rat hepatocytes to catechin (0.01-1.0 mM), a plant phenolic flavonoid, and subsequent addition of 2-acetylaminofluorene (AAF) resulted in an enhanced binding of AAF metabolites to hepatocellular DNA. Incubations of hepatocytes with catechin and S. typhimurium demonstrated no mutagenicity of catechin. At 1.0 and 5.0 mM concentrations of catechin with AAF and 30-min incubation with hepatocytes prior to plating there was inhibition of AAF-induced mutagenicity. However, at 0.5 mM of catechin there was a significant enhancement in mutagenicity. The increase in DNA binding of AAF in the cultures of hepatocytes is due to the alteration of metabolism by exposure to catechin. Catechin increases both N-hydroxylation and deacetylation pathways in the hepatocytes producing increases in N-hydroxy-AAF and aminofluorene. Both of these metabolites are important in AAF intermediates binding with DNA. The short-term incubation of catechin, AAF, hepatocytes, and S. typhimurium in the mutagenesis assay is not sufficient for induction of metabolic pathways. However, previously reported inhibition of detoxification pathways and/or scavenging of the proximate carcinogen can occur to alter mutagenesis in a dose-dependent manner.
Monteith
D K
DK
Department of Biological Sciences, Indiana University, Purdue University, Fort Wayne 46805-1499.
D015073:2-Acetylaminofluorene / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D002392:Catechin / Q000494:pharmacology*; D002469:Cell Separation; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008297:Male; D009153:Mutagens / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects
D009153:Mutagens; D002392:Catechin; D004247:DNA; D015073:2-Acetylaminofluorene