Teratogenesis, Carcinogenesis, and Mutagenesis 17:45–58 (1997) © 1997 Wiley-Liss, Inc. Modulating Effects of Flavonoids on Food Mutagens in Human Blood and Sperm Samples in the Comet Assay Diana Anderson, 1 * Nurs¸en Basaran, 2 Malgorzata M. Dobrzyn ´ska, 3 Ahmet A. Basaran, 2 and Tian-Wei Yu 1 1 Department of Genetic and Reproductive Toxicology, BIBRA International, Carshalton, Surrey, United Kingdom 2 Faculty of Pharmacy, Hacettepe University, Ankara, Turkey 3 Department of Radiation Protection and Radiobiology, National Institute of Hygiene, Warsaw, Poland The flavonoids silymarin, myricetin, quercetin, kaempferol, rutin, and kaempferol-3- rutinoside have been examined in combination with the food mutagens 3-amino-1- methyl-5H-pyrido (4,3-b)indole (Trp) and 2-amino-3-methylimidazo-4,5-f)quinoline (IQ) in the Comet assay in human lymphocytes from donors A and B and human sperm from donor B. These compounds alone have been shown to produce positive responses in the Comet assay, as have the food mutagens. However, in combination with the food mu- tagens, the flavonoids produced antigenotoxic effects since DNA damage was reduced in the Comet assay in human lymphocytes and sperm over a similar dose range in the absence of metabolic activation. Only quercetin and kaempferol were examined in blood with metabolic activation, but there was no difference in response to that obtained with- out activation. In the blood there was an exacerbation or synergy of response at the low- est doses of the flavonoids. In the sperm this was also the case with silymarin and myricetin. With kaempferol there was no antigenotoxic effect and quercetin protected below base- line levels. Since the effects were observed in lymphocytes and sperm over a similar dose range, it would suggest that the Comet assay responses occur in somatic and germ cells in a one-to-one ratio. These results have implications for man in terms of risk assessment and in the modulation of isolated food constituents. Teratogenesis Carcinog. Mutagen. 17:45–58, 1997. © 1997 Wiley-Liss, Inc. Key words: Trp; IQ; silymarin; myricetin; quercetin; kaempferol; rutin; kaempferol-3-rutinoside INTRODUCTION It has been known for some time that a variety of potential mutagens and anti- mutagens are present in extracts from higher plants. Omnivorous and herbivorous *Correspondence to: Dr. D. Anderson, BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS, United Kingdom.