Comparative metabolism of 7H-dibenzo[c,g]carbazole and dibenz[a,j]acridine by mouse and rat liver microsomes.
The comparative metabolism of the carcinogenic pollutants 7H-dibenzo[c,g]-carbazole (DBC) and dibenz[a,j]acridine (DBA) was investigated in vitro using 3-methylcholanthrene (3MC) induced Sprague-Dawley rat and Hsd:ICR(Br) mouse liver microsomal preparations with benzo[a]pyrene (BaP) as the positive control. Metabolites were isolated and separated by HPLC and identified by spectroscopic and co-chromatographic techniques using synthetic standards. The major metabolites of DBC were the phenols: the 5-OH-DBC, 3-OH-DBC, and 2-OH-DBC. Traces of 1-OH-DBC were also found yet no dihydrodiols were identified. The major metabolites of DBA were the 3,4-diol-DBA and 5,6-diol-DBA, 1,2-diol-DBA, DBA-5,6-oxide and 4-OH-DBA. Treatment of both mice and rats with 3MC resulted in significant (P less than or equal to 0.05) increases relative to control in the microsomal metabolism of DBA to dihydrodiol and phenol metabolites, similar to that observed for BaP. 3MC-induced rat liver microsomes significantly (P less than or equal to 0.05) increased DBC metabolism relative to control microsomes whereas DBC metabolism was not increased with 3MC-induced mouse liver microsomes. These data indicate that different enzymatic pathways are involved in the metabolic activation of DBC in the Hsd:ICR(Br) mouse and Sprague-Dawley rat.
Wan
L P
LP
Department of Environmental Health, University of Cincinnati Medical Center, OH 45267-0056.
Xue
W L
WL
Schneider
J
J
Reilman
R
R
Radike
M
M
Warshawsky
D
D
D000166:Acridines / Q000378:metabolism*; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D001564:Benzo(a)pyrene / Q000378:metabolism; D001711:Biotransformation; D002227:Carbazoles / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002273:Carcinogens / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D008862:Microsomes, Liver / Q000378:metabolism*; D011865:Radioisotope Dilution Technique; D051381:Rats; D011919:Rats, Inbred Strains
D000166:Acridines; D002227:Carbazoles; D002250:Carbon Radioisotopes; D002273:Carcinogens; C022289:dibenzacridine; D001564:Benzo(a)pyrene; D008748:Methylcholanthrene; D001189:Aryl Hydrocarbon Hydroxylases; C013478:7H-dibenzo(c,g)carbazole