Protection by chlorophyllin against the covalent binding of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) to rat liver DNA.
Chlorophyllin (CHL), a sodium/copper salt of chlorophyll used in the treatment of geriatric patients, exhibits potent antimutagenic activity in a range of assays in vitro and in vivo. The protective effects of CHL were studied in Sprague-Dawley rats using inhibition of carcinogen-DNA binding as an end-point. Animals were administered CHL (150 mg/kg body wt) and [2-14C]2-amino-3-methylimidazo[4,5-f]quinoline (IQ, 50 mg/kg body wt) by single oral gavage. Covalent IQ-DNA binding in liver was determined 8, 24 and 48 h after dosing; CHL inhibited binding at these times by 58, 56 and 46% respectively, compared with rats given IQ alone. The total liver burden of IQ-derived radioactivity was reduced in CHL-treated rats, as was the total amount of radiolabel eliminated in the urine and bile. However, elimination via the feces was increased in rats given CHL, both in terms of total radiolabel eliminated and amount of unmetabolized IQ in dichloromethane extracts of feces. Finally, pretreatment with CHL in the drinking water, or injection of CHL into isolated loops of intestine in situ, reduced the absorption of IQ from the gut. Collectively, these findings indicate that, when administered simultaneously with the carcinogen, CHL attenuates IQ-DNA binding in rat liver by interacting with IQ in the gut and reducing carcinogen uptake, distribution and metabolism. The results suggest that further studies should be conducted with respect to the protective mechanisms and possible anti-carcinogenic properties of CHL.
Dashwood
R H
RH
Department of Environmental Biochemistry, University of Hawaii, Honolulu 96822.
D000818:Animals; D001646:Bile / Q000378:metabolism; D002273:Carcinogens / Q000378:metabolism*; D002735:Chlorophyllides / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism*; D005243:Feces / Q000737:chemistry; D008099:Liver / Q000378:metabolism*; D008297:Male; D009153:Mutagens / Q000378:metabolism*; D011804:Quinolines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D002273:Carcinogens; D002735:Chlorophyllides; D009153:Mutagens; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D004247:DNA; C007020:chlorophyllin