Report on the mutagenicity of flavone derivatives and their contribution to advancing scientific knowledge

Flavonoids, such as quercetin and kaempferol, and their glycosides, are widely distributed in vegetables and fruits. Sugimura, T. et al. investigated the mutagenicity of flavone derivatives, and found that quercetin and kaempferol showed high mutagenic activities in Salmonella typhimurium TA98 with S9 mix, comparable to that of the typical carcinogen, benzo[a]pyrene. These novel findings were published in Proc. Jpn. Acad. Ser. B 53, 194-197, 1977. Other research groups also reported the mutagenic properties of flavone derivatives in S. typhimurium strains. These observations led to the commencement of long-term animal carcinogenesis experiments involving quercetin. A USA-Turkey joint study reported that feeding rats with 0.1% quercetin in the diet produced carcinomas. However, Japanese scientists showed no carcinogenicity with quercetin in rats, mice, or hamsters, even at 10% in the diet. NTP Technical Report on the Toxicology and Carcinogenesis Studies of Quercetin in F344/N Rats concluded that there was no evidence of its carcinogenic activity. Therefore, the potential risk of quercetin in human cancers is likely to be negligible. These flavonoid issues provided a warning regarding the simplistic understanding that mutagens are carcinogens, and microbial tests alone are inadequate for safety assessment; therefore, and a battery of tests for genotoxicity is recommended. Thus, the informative report in 1977 made significant contributions to initiating and promoting genotoxicity studies of flavonoids.