Evaluation of the antimutagenic potential of anthracene: in vitro and ex vivo studies.
The present study was undertaken in order to evaluate the in vitro and ex vivo antimutagenicity of anthracene against the food-borne carcinogen IQ (2-amino-3-methylimidazo[4,5-f]quinoline). Anthracene caused a marked, concentration-dependent decrease in the mutagenicity of IQ in the Ames test, whether hepatic S9 or isolated microsomes from Aroclor 1254-induced rats served as the activation systems. Anthracene gave rise to a concentration-dependent inhibition of the 0-deethylation of ethoxyresorufin, a diagnostic probe for CYP1A (cytochrome P450 family 1, subfamily A) activity, and of the metabolic activation of Glu-P-1 (2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole, a diagnostic probe for CYP1A2. When microsomal metabolism of IQ was terminated by menadione, incorporation of anthracene into the incubation mixture once again inhibited the mutagenicity of IQ. All the above observations indicate that anthracene owes its antimutagenic response against IQ to: (a) inhibition of its CYP1A-mediated activation and (b) direct interaction between anthracene and the reactive intermediate(s) of IQ leading to their inactivation. Treatment of rats with anthracene did not greatly influence the ability of hepatic preparations to bioactivate IQ to mutagens. Similarly, administration of anthracene 2 h before sacrifice to Aroclor 1254-pretreated rats, did not modulate the hepatic activation of IQ. These findings demonstrate that the in vitro mechanisms of the antimutagenicity of anthracene are not operative in vivo, and further illustrate the inadequacy of in vitro studies, conducted in isolation, in predicting such effects.
Bu-Abbas
A
A
Division of Toxicology, School of Biological Sciences, University of Surrey, Guildford, UK.
Ioannides
C
C
Walker
R
R
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology*; D016587:Antimutagenic Agents / Q000494:pharmacology*; D001711:Biotransformation; D002273:Carcinogens / Q000633:toxicity; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D007093:Imidazoles / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism; D011804:Quinolines / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics
D000873:Anthracenes; D016587:Antimutagenic Agents; D002273:Carcinogens; D065607:Cytochrome P-450 Enzyme Inhibitors; D007093:Imidazoles; D009153:Mutagens; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; C023785:2-amino-6-methyldipyrido(1,2-a-3',2'-d)imidazole; D003577:Cytochrome P-450 Enzyme System; C034020:anthracene