Promutagen activation by rodent-liver postmitochondrial fractions in the L5178Y/TK cell mutation assay.
Individual S9 microsomal fractions prepared from normal livers of 8 rodent species or strains and from 1 rat strain pretreated with Aroclor 1254, were used to metabolize the promutagens N-acetyl-2-aminofluorene, 1,2-benzanthracene, benzo[a]pyrene, and 3-methylcholanthrene to active forms during 3-h co-incubation in the presence of L5178Y/TK+/- cells. The 8 compatible S9 preparations all converted each of the 4 chemical carcinogens into active mutagens with varied efficiencies except for the Aroclor-induced rat S9/benzanthracene combination which produced only weak activity. Aroclor induction did not notably enhance the mutagenicity of benzo[a]pyrene or 3-methylcholanthrene beyond that activity mediated by the other non-induced preparations. Syrian hamster S9 and, to a lesser degree, C57BL/6J mouse S9 were exceptionally active in converting N-acetyl-2-aminofluorene to toxic and mutagenic metabolites. One source of Swiss mouse liver (Blu : Ha ICR) provided the most active S9 when tested with the 3 polycyclic aromatic hydrocarbons. In general, mutagenicity and cytotoxicity were roughly correlated within S9 + promutagen combinations. Almost all of the methylcholanthrene metabolizing activity was lost by the 12th week when Aroclor-induced rat S9 was held at -20 degrees C, yet this activity remained constant when similar S9 was stored at -80 degrees C for 14 weeks. Surprisingly, some S9 sources including the induced rat-liver preparation converted anthracene to a weak or border-line mutagen. The activation of both 1,2-benzanthracene and anthracene may be linked within each species or strain although Aroclor induction enhanced anthracene mutagenicity yet attenuated the mutagenicity of 1,2-benzanthracene. Collectively, these data underscore the current inchoate state of development for S9 coupled somatic cell mutation assays.
D000818:Animals; D000873:Anthracenes / Q000378:metabolism; D001140:Aroclors / Q000494:pharmacology; D001551:Benz(a)Anthracenes / Q000378:metabolism; D001711:Biotransformation; D002460:Cell Line; D006224:Cricetinae; D008223:Lymphoma; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism*; D051381:Rats; D013045:Species Specificity
D000873:Anthracenes; D001140:Aroclors; D001551:Benz(a)Anthracenes; D009153:Mutagens