Drug Metab Dispos. 2000 Nov;28(11):1297-302.  

Prenylflavonoids from hops inhibit the metabolic activation of the carcinogenic
heterocyclic amine 2-amino-3-methylimidazo[4, 5-f]quinoline, mediated by
cDNA-expressed human CYP1A2.

Miranda CL, Yang YH, Henderson MC, Stevens JF, Santana-Rios G, Deinzer ML,
Buhler DR.

Department of Environmental and Molecular Toxicology, Oregon State University,
Corvallis, Oregon 97331-7301, USA.

The heterocyclic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) is a
potential human carcinogen found in cooked food that requires initial metabolic
activation by cytochrome P450s, primarily CYP1A2. The present study was
conducted to examine whether recombinant human CYP1A2 expressed in insect cells
mediates the metabolic activation of IQ and whether prenylflavonoids found in
hops and beer would modulate the CYP1A2-mediated activation of IQ. The
cDNA-expressed human CYP1A2 was found to strongly activate IQ as measured by the
Ames Salmonella assay and by the covalent binding of IQ metabolites to calf
thymus DNA and protein. Inhibition studies showed that the prenylchalcone
xanthohumol and the prenylflavanones 8-prenylnaringenin and isoxanthohumol
strongly inhibited the mutagenic activation of IQ mediated by cDNA-expressed
human CYP1A2 in the Ames Salmonella assay. The three prenylflavonoids also
markedly inhibited the human CYP1A2-mediated binding of IQ to metabolites that
bind to DNA. The inhibition of the metabolic activation of IQ was paralleled by
the inhibition of acetanilide 4-hydroxylase activity of human CYP1A2. Thus,
xanthohumol, isoxanthohumol, and prenylflavanones 8-prenylnaringenin are potent
inhibitors of the metabolic activation of IQ and may have the potential to act
as chemopreventive agents against cancer induced by heterocyclic amines
activated by CYP1A2.

PMID: 11038156 [PubMed - indexed for MEDLINE]