ABSTRACTThebiologicalactivitiesofseveralepoxideanddihydroderivativesofchryseneandphenanthrenewereevaluatedbyrnutagenicitystudieswithbacterialandmammaliancellsandskintumorigenicitystudieswithmice.InstrainsTA98andTA100ofSalmonellatyphimurium,thebay-region(±)-1/S,2a-dihydroxy-3a,4a-epoxy-7,8,9,10-tetrahydrochrysene withthebenzylic1-hydroxygroupfranstothebay-regionepoxideoxygenwassixandfourtimesmoremutagenic,respectively,thanwasitsdiastereomer(±)-1/S,2a-dihydroxy-3/8,4/S-epoxy-1,2,3,4-tetrahydrochrysene andwasover40timesmoremutagenicthanwastheK-regionchrysene5,6-oxide.Similarly,inChinesehamsterV79cells,(±)-1/8,2a-dihydroxy-3a,4a-epoxy-7,8,9,10-tetrahydrochrysene wasfourtimesmoremutagenicthanwas(±)-1/3,2o-dihydroxy-3/S,4/8-epoxy-1,2,3,4-tetrahy-drochrysene.Chrysene5,6-oxide,althoughcytotoxic,wasonlyveryweaklymutagenic.Thebay-regiontetrahydroepoxideofchrysene,3,4-epoxy-1,2,3,4-tetrahydrochrysene, wasthemostmutagenicchrysenederivativeexaminedinbothbacterialandmammaliancellsandwasfromsixtoeighteentimesmoreactivethanwasthenon-bay-regiontetrahydroepoxide, 1,2-epoxy-1,2,3,4-tetrahydrochrysene. 1,2-Dihydrochrysene, apotentialmetabolicprecursorofthebay-regiontetrahydroepoxidewasmetabolizedtohighlymutagenicproducts,and3,4-epoxy-1,2,3,4-tetrahydrochrysene and1,2-dihydrochry-senewerebothastumorigenicaschryseneonmouseskin.Thediastereomericbay-regiondiol-epoxidesofphenanthreneexhibiteddose-dependentmutagenicactivityinstrainsTA98andTA100ofSalmonellatyphimurium,althoughtheywerelessactivethanwasthecorrespondingbay-regiondiol-epoxidesofchrysene.(±)-1/8,2a-Dihydroxy-3a,4a-epoxy-1,2,3,4-tetrahydrophenanthrene wasmoremutagenicinstrainTA100andintheChinesehamsterV79cellsthanwasitsdiastereomer,(±)-1/S,2a-dihydroxy-3/S,4/8-epoxy-1,2,3,4-tetrahydrophenanthrene. Thesetwodiol-epoxideshadlowbutessentiallyequivalentactivityinstrainTA98.Thebay-region3,4-epoxy-1,2,3,4-tetrahydrophenanthrene wasfromseventosixtytimesmoremutagenicthanwas(±)-1/3,2a-dihydroxy-3a,4a-epoxy-1,2,3,4-tetrahydrophenanthrene inbacterialandmammaliancellsandwasfrom8to17timesmoremutagenicthanwas1,2-epoxy-1,2,3,4-tetrahydrophenanthrene, thenon-bay-regiontetrahydroepoxideofphenanthrene.Although1,2-dihydrophenanthrene,thepotentialmetabolicprecursorofthemutagenicbayregiontetrahydro-3,4-epoxideofphenanthrene,wasmetabolicallyactivatedtomutagenicproductsbyratlivermicrosomes,neitherphenanthrenenorthethreemetabolicallypossiblefrans-dihydrodiolsofphenanthrenewasmetabolizedtobacterialmutagens.Ininitiation-promotionexperimentsonmouseskin,phenanthrene,1,2-dihydrophenanthrene,andthethreemetabolicallypossibletrans-dihydrodiolsofphenanthrenepossessedlittleornotumorigenicactivityatahighinitiatingdoseof10/imol.Thebay-regiontetrahydro-3,4-epoxide,whichwasthemostmutagenicderivativeofphenanthreneinbacterialandmammaliancells,hadsignificanttumorigenicactivityonmouseskin.INTRODUCTIONPhenanthreneisthesimplestexampleofanangular(nonlinear)polycyclicaromatichydrocarbonwhichhasabayregion.Althoughphenanthreneisgenerallyconsideredtobeinactiveasacarcinogen(6),fusionofabenzoringatthe1,2-positionproducesthehydrocarbonchrysenewhichhasweakbutsignificantcarcinogenicactivity(6,15).Inaccordancewiththequantummechanicalpredictionsofthebay-regiontheory(10),thechemicalreactivitiesofthebay-region1,2-diol-3,4-epox-idesofphenanthrene(AEdeioc/AŸ=0.658)andofchrysene(AEdeioc//S=0.639)aresimilar.These1,2-diol-3,4-epoxidesareproposedbythebay-regiontheorytobethebestcandidatesforultimatecarcinogenicandmutagenicmetabolitesofbothhydrocarbons.Thepresentstudycomparesthebiologicalactivitiesofphenanthreneanditsderivatives(Chart1)withthoseofchryseneanditsderivatives(Chart2).Previousstudiesofthemetabolicactivationofthe3possible1,2-,3,4-,and5,6-dihydrodiolsofchrysene2havedemonstratedthatonlythe1,2-dihydrodiolcouldbemetabolicallyactivatedtohighlymutagenicproducts(27).The2-to3-foldgreaterskintumorincidenceofthisdihydrodiolrelativetothatofchryseneindicatesthatitisaproximatecarcinogenofchrysene(15).When thedoublebondin 3,4-positionofchrysene1,2-dihydrodiolissaturated,theresultingtetrahydro-diolhasgreatlydiminishedmutagenic(27)andtumorigenic