PROTECTION BY GREEN TEA, BLACK TEA, AND INDOLE-3-CARBINOL AGAINST 2-AMINO-3-METHYLIMIDAZO[4,5-F]QUINOLINE-INDUCED DNA-ADDUCTS AND COLONIC ABERRANT CRYPTS IN THE F344 RAT
M. Xu et al., PROTECTION BY GREEN TEA, BLACK TEA, AND INDOLE-3-CARBINOL AGAINST 2-AMINO-3-METHYLIMIDAZO[4,5-F]QUINOLINE-INDUCED DNA-ADDUCTS AND COLONIC ABERRANT CRYPTS IN THE F344 RAT, Carcinogenesis, 17(7), 1996, pp. 1429-1434
Male F344 rats were exposed for 8 weeks to extracts of green tea (2% w
/v) or black tea (1% w/v), or to 0.1% dietary indole-3-carbinol (I3C),
In weeks 3 and 4 of the study, rats were given 2-amino-3-methylimidaz
o[4,5-f]-quinoline (IQ) every other day by oral gavage (50 mg/kg body
wt) in order to induce aberrant crypt foci (ACF) in the colon. Compare
d with controls given IQ alone, all three inhibitors reduced the numbe
r of total aberrant crypts per colon, and green tea and I3C inhibited
significantly the mean number of ACF (P < 0.05), Rats pre-treated with
green tea, black tea, or I3C and given a single p.o. injection of 50
mg IQ/kg body wt 24-48 h before sacrifice had reduced levels of IQ-DNA
adducts in the liver, and excreted lower amounts of IQ and other prom
utagens in the urine and feces, Inhibitors also reduced the excretion
of IQ-sulfamate in the urine, but increased the relative amounts of IQ
-5-O-sulfate and IQ-5-O-glucuronide. Western blotting together with as
says for 7-ethoxyresorufin O-deethylase and methoxyresorufin O-demethy
lase established that I3C preferentially induced cytochrome P4501A1 ov
er 1A2, consistent with the altered profile of urinary metabolites, Ho
wever, both teas caused slight induction of cytochrome P4501A2 versus
1A1, which would be predicted to enhance the activation of IQ, Thus, g
reen tea and black tea are likely to protect against IQ-DNA adducts an
d ACF by mechanisms other than induction of cytochromes P450, such as
inhibition of enzymes which activate IQ or the scavenging of reactive
intermediates.