The antimutaqenicity of the Citrus flavonoids naringin, hesperidin, no
biletin, and tangeretin against the mutagens benza[a]pyrene, 2-aminofl
uorene, quercetin, and nitroquinoline N-oxide was investigated in the
Salmonella/microsome assay. Naringin and hesperidin showed a weak anti
mutagenic activity against benzo[a]pyrene. Tangeretin was antimutageni
c against all indirectly-acting mutagens tested, but in general a larg
e molar excess was necessary. Liquid preincubation increased the antim
utagenicity of tangeretin against 2-aminofluorene. Nobiletin acted as
an antimutagen against benzo[a]pyrene, but it enhanced the mutagenicit
y of 2-aminofluorene. However, in a liquid preincubation assay nobilet
in also exhibited antimutagenicity against 2-aminofluorene. Both tange
retin and nobiletin inhibited the mutagenicity of quercetin. Quercetin
itself acted as an antimutagen against 2-aminofluorene in a Salmonell
a strain (TA1538) where its mutagenicity was not expressed. Quercetin
should not merely be regarded as a genotoxic risk factor in the human
diet, since its mutagenicity may be inhibited by accompanying compound
s including other flavonoids, and since quercetin itself also exhibits
an antimutagenic action. Because of the antimutagenic properties the
Citrus flavonoids tested, especially tangeretin and nobiletin, might p
lay a role in the chemoprevention of cancer.