Flavonoids modulate comet assay responses to food mutagens in human lymphocytes and sperm.
The flavonoids, silymarin, myricetin, quercitin, 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-P-2) and 2-amino-3-methylimidazo-(4,5-f) quinoline (IQ), in the Comet assay in human lymphocytes from donor A 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 mutagens, the flavonoids produced antigenotoxic effects since DNA damage was reduced in the Comet assay in lymphocytes and sperm. The assays were performed in the absence of metabolic activation, since when quercetin and kaempferol were examined in blood with metabolic activation, there was little or no difference in response to that obtained in its absence. In the blood, there was an exacerbation or synergy of response at the lowest doses of the flavonoids. In the sperm, with silymarin, myricetin and quercitin, antigenotoxic effects only were observed, but with kaempferol, in general, there were no protective effects. The food mutagen, 2-amino-1-methyl-6-phenylimadazo (4,5-b)pyridine (PhIP), was also examined in addition to Trp-P-2 and IQ in combination with silymarin and myricetin in donors A and C in human lymphocytes only. Similar exacerbation of effects were found at low doses of these flavonoids with antigenotoxic effects at high doses. This was confirmed in the Ames test. There were slightly different profiles in lymphocytes and sperm, but antigenotoxic effects were observed over a similar dose range. This would suggest that effects occur in somatic and germ cells on a one-to-one ratio. These results have implications for man in terms of risk assessment and in the modulation of isolated food constituents.
BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK.
D
D
Anderson
M M
MM
Dobrzyńska
N
N
Başaran
A
A
Başaran
T W
TW
Yu
D000328:Adult; D016587:Antimutagenic Agents / Q000494:pharmacology*; D002243:Carbolines / Q000633:toxicity; D004586:Electrophoresis / Q000379:methods; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009153:Mutagens / Q000633:toxicity*; D011804:Quinolines / Q000633:toxicity; D013094:Spermatozoa / Q000187:drug effects*
D016587:Antimutagenic Agents; D002243:Carbolines; D005419:Flavonoids; D009153:Mutagens; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; C019133:3-amino-1-methyl-5H-pyrido(4,3-b)indole