The mutagenicity of chemically synthesized metabolites of 16,17-dihydro-15H-cyclopenta[a]phenanthrene and its carcinogenic 11-methyl homologue.
Putative synthetic metabolites of the hydrocarbon 16,17-dihydro-15H-cyclopenta[a]phenanthrene and its carcinogenic 11-methyl analogue, namely trans-3,4-dihydroxy-3,4,16,17-tetrahydro-15H- cyclopenta[a]phenanthrene and its 11-methyl derivative, together with the four associated trans-3,4-dihydroxy-syn- and anti-1,2-epoxides, were assayed for mutagenicity in the Ames test with Salmonella typhimurium TA100 with and without microsomal activation. The hydrocarbons were weakly mutagenic and the 3,4-diols were more strongly so, but all required activation to express their mutagenic potential. All four diol-epoxides were much more potent mutagens, even in the absence of activation. This is in accord with the anticipated metabolic activation sequence: hydrocarbons-->3,4-diols-->3,4-diol-1,2-epoxides.
Department of Chemistry, School of Biological Sciences, University of Surrey, Guildford, UK.
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Papaparaskeva-Petrides
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Ioannides
G W
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Boyd
R J
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Young
R G
RG
Harvey
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Coombs
D000818:Animals; D002273:Carcinogens; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens; D010616:Phenanthrenes / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013329:Structure-Activity Relationship
D002273:Carcinogens; D009153:Mutagens; D010616:Phenanthrenes