Protective properties of chlorophylls against the covalent binding of heterocyclic amines to DNA in vitro and in vivo.
The protective properties of chlorophylls have been studied using inhibition of carcinogen-DNA binding as an end point. Rats were co-administered sodium/copper chlorophyllin (CHL) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) by single oral gavage. Eight hours after dosing, CHL inhibited IQ-DNA binding in liver by approximately 60% compared with rats given IQ alone. CHL treatment reduced the total radiolabel eliminated in urine and bile but caused increased excretion via the feces, including enhanced elimination of unmetabolized IQ. In a second study, CHL produced dose-related inhibition of IQ-DNA binding in the liver, large intestine and small intestine, and blocked IQ absorption from ligated sections of the intestine in situ. In in vitro studies CHL competitively inhibited microsome-mediated IQ-DNA binding, and interacted with liver microsomes to produce a difference spectrum with a peak at approximately 420 nm and a trough at 383 nm. CHL also interacted directly with heterocyclic amines to form 2:1 (IQ-type) or 1:1 complexes (non-IQ-type) with dissociation constants in the range 0.333 to 0.083 mM. Finally, in hepatocytes chlorophyll a inhibited the metabolism of 3-amino-1-methyl-5H-pyrido [4,3-b]indole (Trp-P-2) and produced dose-related inhibition of Trp-P-2-DNA binding. Collectively, these studies suggest that chlorophylls operate as interceptor molecules and limit carcinogen bioavailability. As a contributing mechanism, chlorophylls may interfere with cytochrome P450-mediated activation of chemical carcinogens.
Dashwood
R
R
Department of Environmental Biochemistry, University of Hawaii, Honolulu 96822, USA.
Guo
D
D
D000284:Administration, Oral; D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D002735:Chlorophyllides / Q000494:pharmacology*; D018736:DNA Adducts / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009153:Mutagens / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D011804:Quinolines / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D016587:Antimutagenic Agents; D002735:Chlorophyllides; D018736:DNA Adducts; D009153:Mutagens; D011804:Quinolines; C007020:chlorophyllin; C036989:2-amino-3,4-dimethylimidazo(4,5-f)quinoline