Measured by the Rate of Eruption of the Incisor of the Mouse

Followinghisdemonstration thatguanineisametabolicrequirement inTetrahymena, Kidder(2)showedthatguaninedeficiency,broughtaboutthroughcompetitiveinhibitionbythestructuralanalogue8-azaguanine,resultedininhibitionofthegrowthofTetrahymena colonies.IthadpreviouslybeenshownbyBrownetal.(1)thatguanineisnotanutritiverequirement forrats.Guaninefedtoratsisnotusedasrawmaterialforthesynthesisofnucleicacidsbutisbrokendownandexcreted(1).Kidderreasonedthat,iftumormetabolismresembledthatofciliatesratherthanthatofnormalmammaliantissues,thenguaninemightbeadietaryrequirement fortumorgrowthand8-azaguaninemightinhibitthegrowthoftumorsbycompetitiveinhibition,whilenotaffectingnormaltissues.Testsinmice(2)showedthatthesubcutaneousorintraperitoneal administration of8-azaguaninehadaverypronounced actioninretardingthegrowthofadenocarcinoma E0771andofseveralothertumors,whilenotseemingtoaffectthehealthofcontrolanimals.Itseemedinteresting,therefore,totestKidder'shypothesisthatthegrowth-inhibiting actionof8-azaguanineislimitedtotumortissue.Forthispurpose,amoresensitivemethodwasrequiredthanthecommonlyusedproceduresoffollowingweightcurvesorofdetermining “therapeuticratiosâ€s(3).Itwashopedthatastudyoftherateofincisoreruptionmightprovetobeabettertool.Asisknown,theincisorsinrodentsarecontinuouslyeruptingteeth.Whiletheperipheral endshearsoff,thesameover-alllengthismaintainedthroughcontinuousgrowthattheopenbasalendandthrougheruptionofthetooth.Therateoferuption,therefore,isadirectmeasureofrateofaTheinvestigationwascarriedoutundercontract#W