Inhibition of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-DNA binding in rats given chlorophyllin: dose-response and time-course studies in the liver and colon

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Abstract
Chlorophyllin (CHL), a water-soluble salt of chlorophyll, has been shown to inhibit 2-amino-3-methylimidazo[4,5-f]quinoline (IO)-DNA binding in vitro by a mechanism that involves molecular complex formation with the carcinogen. Based on this mechanism, rats weighing ∼160 g were given 10 μmol (100 μCi) IQ or IQ plus 20, 200 or 1000 μmol CHL by single oral gavage. Six hours after dosing, CHL produced dose-related inhibition of IQ-DNA binding in three target organs for cardnogenesis, namely, the small intestine, large intestine and liver. In the latter tissues, >80% inhibition was detected at the highest CHL dose tested, while IQ-DNA binding levels in the small intestine were reduced to below the limit of detection. Co-injection of CHL and IQ into ligated sections of small intestine inhibited the absorption of IQ in a dose-related manner, such that the highest dose of CHL almost completely blocked carcinogen uptake. Finally, rats given CHL by gavage at time 0 h were treated with IQ at various times thereafter and IQ-DNA binding levels were measured in the liver and colon 6 h after carcinogen exposure. Compared with controls given IQ alone, CHL inhibited binding by 79% at 0 h and 40% at 1 h in the liver, and by 63% at 0 h,38% at 1 h and 58% at 24 h in the colon (P < 0.05 by Student's t-test). These results support a mechanism involving complex formation between CHL and IQ in vivo and suggest that the inhibitor is likely to be most effective when ingested simultaneously with the carcinogen.

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