日本化学療法学会雑誌第55巻第S-1号

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1 Key words I

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4 Table. FertilitydataonmaleratstreatedoralywithGRNXinthestudyoffertilityandearlyembryonic developmenttoimplantation No.ofmaleratsexamined Copulationrate(%) Impregnationrate(%) No.ofsperms( 6 /gcauda) Motilityofsperms(%) Swimmingspeedofsperms (μ m/sec.) Abnormalsperm ratio(%) ±.5 88.±..8±.5.± ±.9 * 9.6±5.8.5±5..6±. 6.9±8. 9.8±7..±8..±. Mean±S.D. Significantdiferencefrom control: *,p<.5(student st-testoraspin-welchtest) ± ±.8.±5. 5.7±8. Table. FertilityandcaesareansectiondataonfemaleratstreatedoralywithGRNXinthestudyof fertilityandearlyembryonicdevelopmenttoimplantation 6 5, No.offemaleratsexamined Estrouscycle(days) Daysfrom matingtocopulation Copulationrate(%) Pregnancyrate(%) No.ofcorporalutea No.ofimplantations Implantationrate(%) No.ofliveembryos Deadorresorbedembryos(%).±..8± ±.6 6.7±.6 8.6±8.5 5.±.9 9.±8..±.7.± ±. 6.±. 8.8±..8±.6 7.5±7..±..±. 9.9±.7 6.9±. 86.±. 5.7±. 7.±6.7.±..8± ±. 6.5±. 8.7±8. 5.6±.9 5.±6.8 Mean±S.D.

5 Table. ReproductivefindingsonratdamstreatedoralywithGRNXinthestudyfor efectsonpre-andpostnataldevelopment,includingmaternalfunction 6 5, No.ofdams Gestationperiod(days) Deliveryrate(%) No.ofimplantations.± ±.9 7.±. 5.±. 9.± ±5. 8.±. 5.±. Mean±S.D. Table. Fofspringdataatbirthandduringlactationperiodobtainedfrom ratdamstreatedoralywithgrnxinthestudyfor efectsonpre-andpostnataldevelopment,includingmaternalfunction Birthrate(%) No.ofliveofspringatbirth Sexratio[Male/(Male+ Female)] ViabilityonDay(%) ViabilityonDay(%) Bodyweight(g) Day (Male/Female) Day Day 7 Day Day (SkeletalobservationonDay) No.offetuseswithskeletalanomalies Fusionofcervicalvertebralarches No.offetuseswithskeletalvariations Cervicalvertebralbody Dumbbelshape Spliting Unilateralformation Thoracicvertebralbody Dumbbelshape 5lumbarvertebrae Sacralization Cervicalrib Lumbarrib Shorteningofthrib Extrasternebrae Degreeofossification 8.±8..7±5..5±.7 99.±.5 99.±.9 7.7/6.7./. 8.69/ / /59. (%) (7.9%) ±9..9±.5.5±.6 98.±.5 ±. 6.97/6.5./.5 8.6/7. 6./.9 6.9/59. (%) (.5%) * ±9.9.±5..5±. 98.8± ± * /6. *. * /9.58 * 7.7 * /6.7 * 5. ** /.7 6. * /56.7 (%) (.6%) Mean±S.D. :Normal. Significantdiferencefrom control: *,p<.5; **,p<.(student st-testoraspin-welchtest) * 7 6, 89.6±7.8.±..8±.8 97.± ± /6.9.79/.6 7.8/ * / /58.5 (.7%) 9(.8%) * *

6 Table5. OrganweightsofFofspringobtainedfrom ratdamstreatedoralywithgrnxinthestudyforefectson pre-andpostnataldevelopment,includingmaternalfunctioninrats (AutopsyonDay) Maingenitalorganweights(g) Male Testis Epididymis Prostate Seminalvesicle Female Ovary Cecum weights(g) Male Female (AutopsyonDay7) Maingenitalorganweights(g) Male Testis Epididymis Female Ovary (Autopsyafterreproductive abilityexamination) Maingenitalorganweights(g) Male Testis Epididymis Female Ovary.±.5.5±.8.±.8.5±.6.8±..5±.7.9±.5.9±.5.9±.66.9±.9.7±.5.6±.7.±.5 6.±..±.7.±.5.±.5.±. **.±..9±.9.9±..888±.8 *.9±..7±.56.5±..±.8 5.±..±.6.±.5.±.5.8±..5±..85±.9.±.5 *.875±.7 *.7±..6±.8.5±.6.6±.5 :Normal. Significantdiferencefrom control: *,p<.5; **,p<.(student st-testoraspin-welchtest),.9±. *.6±.7.±.7.5±.6.8±..6±.6 **.6±. **.8±. **.87±.57 **.±.6.58±.7.8±.99 **.5±.5 Table6. FertilityandcaesareansectiondataonFofspringandFfetaldataobtainedfrom ratdamstreatedoraly withgrnxinthestudyforefectsonpre-andpostnataldevelopment,includingmaternalfunctioninrats Copulationrate Male Female Impregnationorpregnancyrate(%) Male Female Daysfrom matingtocopulation(female) No.ofcorporalutea No.ofimplantations Implantationrate(%) No.oflivefetuses No.ofdeadfetuses Earlystage Latestage Deadfetuses(%) Sexratio[Male/(Male+ Female)] Bodyweight(g) Male Female No.ofFfetuseswithexternalanomalies Dwarf Edema Micrognathia Imperforateanus Brachyury Filamentoustail ±. 9.5±. 6.9±.9 87.±. 5.9±..±..±..±. 6.±7..5±.5.7±..±.8 (.%) 6.8±. 9.9±. 6.±.8 8.7±7..7±.6.6±.5.6±.5.±. 9.±8..9±..±. *.±. ** (.7%) ±..±.6 7.± ±.7 6.7±.5.5±.7.5±.7.±..±.7.5±..±..8±. (.%) Mean±S.D. Significantdiferencefrom control:,p<.5(mann-whitneyu-test) Significantdiferencefrom control: *,p<.5; **,p<.(student st-testoraspin-welchtest), ±.9.±5. 6.±. 77.±7. 5.±.5.9±..8±..±. 5.±6..5±..5±.6.6±.5 (.%)

7 5 Body weight (g) 5 5 GRNX 6 mg/kg GRNX 5 mg/kg GRNX, mg/kg Administration Day of gestation Fig.. BodyweightchangesduringthegestationperiodofdamstreatedoralywithGRNXin thestudyforefectsonembryo-fetaldevelopmentinrats. Significantdiferencefrom control: *,p<.5(student st-testoraspin-welchtest). Table7. CaesareansectiondataonratdamstreatedoralywithGRNXinthestudyforefects onembryo-fetaldevelopment 6 5, No.ofdams No.ofcorporalutea No.ofimplantations Implantationrate(%) No.oflivefetuses No.ofdeadfetuses Earlystage Latestage Deadfetuses(%) Sexratio [Male/(Male+ Female)] Bodyweight(g) Male Female 8 8.±.6.9±. 8.8±..8±.9.±..±..±. 6.8± 7..8±.7.6±..± ±.9 5.5±. 8.9± 9.6.8±..7±.8.7±.8.±..± 5..7±.5.6±.6.± ±.9 5.±. 8.8±.6.7±..8±..8±..±. 5.± 6.9.5±..9±.6.± ±.6.7±.8 8.±.5.9±.6.7±.9.7±.9.±..6± 5.5.5±.8.±..7±.8 Mean± S.D.

8 Table8. External,skeletalandvisceralobservationoffetusesobtainedfrom ratdamstreatedoralywithgrnxinthestudyfor efectsonembryo-fetaldevelopment No.offetuseswithexternalanomalies Dwarf Anophthalmia Kinkedtail No.offetuseswithskeletalanomalies Fusionofexoccipitalbone andcervicalvertebralarch Fusionofsternebrae No.offetuseswithskeletalvariations Thoracicvertebralbody Spliting Dumbbelshape Unilateralformation Unossification 5lumbarvertebrae Sacralization Cervicalrib Lumbarrib Shorteningofthrib Sternebra Asymmetry Spliting Degreeofossification No.offetuseswithvisceralanomalies Situsinversusviscerum totalizes Dilatationoflateralventricle Malpositionofpituitarygland anddeformityofthirdventricle Anophthalmia Thymicremnantinneck Dilatationofrenalpelvis Dilatationofrenalureter Aplasiaoftestisandepididymis (.%) (%) (8.7%) 8(6.9%) 7 6 (%) (%) 6(.8%) 5 * (.9%) :Normal Significantdiferencefrom control: *,p<.5(student st-testoraspin-welchtest) 5 (.%) (%) (6.6%) * (9.8%) 8, (%) (.6%) (.%) 7 5 (8.%) 5

9 Table9. CaesareansectiondataonrabbitdamstreatedintravenouslywithGRNXinthestudyforefects onembryo-fetaldevelopment No.ofdams No.ofdied No.ofabortion No.ofcorporalutea No.ofimplantations Implantationrate(%) No.oflivefetuses No.ofdeadfetuses Earlystage Latestage Deadfetuses(%) Sexratio [Male/(Male+ Female)] Bodyweight(g) Male Female 9.6±. 9.± ± ±.7.6±..±.5.±.8 6.±..5±.5 6.± ± ±. 8.±. 8.9± ±.7.6±.9.±.5.±.6 5.6± 8..5±.8 5.± ± a).6±. 8.±.8 78.±. 7.±.9 *.±..±.6.8±..5±.8.5±.7 6.8± ± 6.66 Mean± S.D. a) :Thenumbercontainsadeadanimal. Significantdiferencefrom control: *,p<.5(student st-testoraspin-welchtest) 5.7±.7 9.5±.9 89.±. 8.±.9.±.6.±.5.9±..± 5.7.5±..5± 5.7.6± 6... Body weight (kg) Administration GRNX 6.5 mg/kg GRNX.5 mg/kg GRNX 5 mg/kg Day of gestation Fig.. Bodyweightchangesduringthegestationperiodofdamstreatedintravenouslywith GRNXinthestudyforefectsonembryo-fetaldevelopmentinrabbits. Significantdiferencefrom control: *,p<.5(student st-testoraspin-welchtest).

10 Table. External,skeletalandvisceralobservationoffetusesobtainedfrom rabbitdamstreatedintravenouslywith GRNXinthestudyforefectsonembryo-fetaldevelopment No.offetuseswithexternalanomalies Forelimbarthrogryposis Omphalocele Brachyury No.offetuseswithskeletalanomalies Fusedsternebrae Sternoschisis Fusedrib Branchedrib Absentrib Nodulatedrib Fusedthoraciccentrum Absentthoracicarch Fusedcaudalvertebrae No.offetuseswithskeletalvariations Accessoryofsternebrae Incompleteossificationofrib Degreeofossification No.offetuseswithvisceralmajoranomalies Rightsubclavianarteryarising from aorticarch Ventricularseptum defect Persistenttruncusarteriosus Diaphragmatichernia Ectopickidney No.offetuseswithvisceralminoranomalies Thymicremnantinneck Supernumerarycoronaryarteryorifice Absentaccessorylobeinlung (.8%) (.5%) (.%) (%) (8.%) (%) (.%) (.8%) (.6%) (.5%) 6 :Normal a) :Theywerelitermates. Significantdiferencefrom control: #,p<.5; ##,p<.(mann-whitneyu-test).5 (.5%) (.5%) (%) (.8%) # (8.5%) (.7%) a) a) a) 8(6.%) # a) a) a) (%) (.5%) a) (.%) ## 6 ## III

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