Microsomal transformation of emodin into a direct mutagen

The activation mechanism of emodin, a fungal anthraquinone and constituent of rhubarb, into a direct mutagen to Salmonella typhimurium TA1537 was investigated by using the S9 and microsomes of rat livers. Upon incubating emodin with the hepatic S9 derived from PCB-pretreated rats, this anthraquinone exhibited mutagenicity in the presence of NADPH or NADH, and this enzymatic activation, maximal at pH 7.0 and occurring in the microsomes, was induced by the pretreatment of rats with PCB, 3-methyl-cholanthrene or phenobarbital and was inhibited by alpha-naphthoflavone, SKF 525A and carbon monoxide. Thin-layer chromatographic analysis revealed that emodin was biotransformed by the microsomal enzymes into at least 5 quinonoid metabolites, among which one pigment, identified as 2-hydroxyemodin (1,2,3,8-tetrahydroxy-6-methyl-anthraquinone), was proved to be a direct mutagen to the test strain, and the remaining 4 quinoniod metabolites were negative or far less active than this active principle.