Identification of the mutagenic metabolites of fluoranthene, 2-methylfluoranthene, and 3-methylfluoranthene.
The metabolites of fluoranthene, 2-methylfluoranthene, and 3-methylfluoranthene obtained upon incubation with liver homogenate from Aroclor pretreated rats were assayed for mutagenicity in Salmonella typhimurium TA100. The mutagenic metabolites of fluoranthene and 2-methylfluoranthene were identified as 2,3-dihydro-2,3-dihydroxyfluoranthene and 4,5-dihydro-4,5-dihydroxy-2-methylfluoranthene, respectively. In contrast to these results, the major proximate mutagen detected among the in vitro metabolites of 3-methylfluoranthene was 3-hydroxymethylfluoranthene. Comparison of the mutagenic potential of 2-hydroxymethylfluoranthene demonstrated that the latter was a more powerful mutagen. Quantitative analyses of the metabolites of fluoranthene with that of 3-hydroxymethylfluoranthene demonstrated that the latter was a more powerful mutagen. Quantitative analyses of the metabolites of fluoranthene, 2-methylfluoranthene, and 3-methylfluoranthene indicated that similar amounts of dihydrodiols were formed. 4,5-Dihydro-4,5-dihydoxy-3-methylfluoranthene, however, was not found to be a potent mutagenic metabolite. These data suggest that the activation pathway to ultimate mutagens may differ for 2- and 3-methylfluoranthene.
D000818:Animals; D001711:Biotransformation; D004785:Environmental Pollutants / Q000378:metabolism*; D005449:Fluorenes / Q000378:metabolism*; D008297:Male; D009153:Mutagens / Q000302:isolation & purification*; D051381:Rats; D011916:Rats, Inbred F344
D004785:Environmental Pollutants; D005449:Fluorenes; D009153:Mutagens; C035918:3-methylfluoranthene; C035917:2-methylfluoranthene; C007738:fluoranthene