TY - JOUR
T1 - Identification of the mutagenic metabolites of fluoranthene, 2-methylfluoranthene, and 3-methylfluoranthene
AU - Lavoie, Edmond J.
AU - Hecht, Stephen S.
AU - Bedenko, Victoria
AU - Hoffmann, Dietrich
N1 - Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 1982
Y1 - 1982
N2 - 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-hydroxymethylfluor-anthene 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.
AB - 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-hydroxymethylfluor-anthene 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.
UR - http://www.scopus.com/inward/record.url?scp=0020315882&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0020315882&partnerID=8YFLogxK
U2 - 10.1093/carcin/3.8.841
DO - 10.1093/carcin/3.8.841
M3 - Article
C2 - 7127666
AN - SCOPUS:0020315882
SN - 0143-3334
VL - 3
SP - 841
EP - 846
JO - Carcinogenesis
JF - Carcinogenesis
IS - 8
ER -