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.
Chlorophyllin (CHL), a water-soluble salt of chlorophyll, has been shown to inhibit 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-DNA binding in vitro by a mechanism that involves molecular complex formation with the carcinogen. Based on this mechanism, rats weighing approximately 160 g were given 10 mumol (100 microCi) IQ or IQ plus 20, 200 or 1000 mumol CHL by single oral gavage. Six hours after dosing, CHL produced dose-related inhibition of IQ-DNA binding in three target organs for carcinogenesis, 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.
Guo
D
D
Department of Environmental Biochemistry, University of Hawaii, Honolulu 96822.
Dashwood
R
R
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002735:Chlorophyllides / Q000494:pharmacology*; D003106:Colon / Q000378:metabolism; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D007408:Intestinal Absorption; D008099:Liver / Q000378:metabolism; D008297:Male; D011804:Quinolines / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D002735:Chlorophyllides; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; C007020:chlorophyllin