`CARCINOGENESIS
`Technical Report Series
`No.42
`1978
`
`BIOASSAY OF
`5-AZACYTI DI N.E
`FOR POSSIBLE CARCINOGENICITY
`
`CAS No. 320-67-2
`
`NCI-CG-TR-42
`
`U.S .. DEPARTMENT OF HEAL TH, EDUCATION, AND WELFARE
`Public Health Service
`National Institutes of Health
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`CELGENE 2023
`APOTEX v. CELGENE
`IPR2023-00512
`
`
`
`BIOASSAY OF
`
`- 5-AZACYTIDINE
`
`FOR POSSIBLE CARCINOGENICITY
`
`Carcinogenesis Testing Program
`Division of Cancer Cause and Prevention
`National Cancer Institute
`National Institutes of Health
`Bethesda, Maryland 20014
`
`U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE
`Public Health Service
`National Institutes of Health
`
`DREW Publication No. (NIH) 78-842
`
`Se.
`Lf 2°1 ;
`-,-y i ·-
`
`
`
`II. MATERI.ALS AND METHODS
`
`A •
`
`. Chemical
`
`5-Azacytidine, which
`
`is a
`
`common name
`
`for 4-amino-l-beta-D(cid:173)
`
`ribofuranosyl-l,3,5-triazipe-2(1H)-one, was obtained as a single
`
`batch
`
`(Lot No. AP-V-128)
`
`from Ash-Stevens,
`
`inc., Detroit,
`
`Michigai;i, by
`
`the Drug Development Branch, Division of Cancer
`
`Treatment, National Cancer Institute (NCI}.
`
`The
`
`identity and purity of
`
`the chemical ~ere confirmed
`
`in
`
`analyses at Stanford Research Institute. Elemental analyses (C,
`
`H, N, 0) were correct ,for C3H1zN405,
`
`the molecular formula of
`
`5- azacytidine.
`
`Infrared, ultraviolet,
`
`and nuclear magnetic
`
`resonance spectra were as expected for
`
`this chemical and were
`
`identical .to spectra of a reference standard. No free 5-azacy(cid:173)
`
`tosine or D-ribose was detected by paper chromatography. On the
`
`oasis of these results, the purity was estimati,!d to be > 99%.
`
`The powdered 5-azacytidine was stored at s0 c in small bottles
`®
`enclosed in sealed plastic bags cont<;1ining Drierite ,·
`
`B, Dosage Preparation
`
`Concentrations of 5-azacytidine of O, l or 0, 2% for rats and O. 02
`
`or O. 04% for mice were prepared in buffered saline (pH 6. 9) for
`
`intraperitoneal injection of
`
`the chemical.
`
`Aqueous solutions
`
`I
`,I
`
`~~-~~~'"""""r,
`.,
`
`3
`
`
`
`were .. not st.ored, beca,us~
`
`th~y are ,unstfb __ le, at roor.1 temperat_ure.
`
`The drug an_d
`
`the vehicle were mixed
`
`in a 10-ml . ~lass Potter..(cid:173)
`
`El°vehjem tissue grinder with a Teflon pestfe. Fresh solutions in
`
`exact a,:iounts for each administrati"on
`
`' • • •
`
`I
`
`..
`were prepared
`
`preceding
`
`injectton. :
`
`C. A~i.mals
`
`Female Sprague-Dawley rats and male and fer.1ale S1.;riss mice were
`
`used in subchr·onic studies.
`
`S,P _rague_-Dawley __ rats and 136C3Fl mice of . both 9exes, oqtain~d
`
`t ,hrou_g.lt . contracts . of the Di.vision of Canc~r Treatment, NC I , were
`
`used in chronic s.tudies:
`
`.The .. Spr:ague.-D?wley rats were obtained
`
`from : Charles River B.reeding Laborato_rie,s, ~nc., Wilmington,
`
`. i·laps_ac.husetts,
`
`and . the B6CJF l mice ·were . obtained fror.1 Charles
`.,
`
`River Laboratqr:~es and from J:,, 1 R. Scl~midt,, Hadipon 1 Wisconsin •
`
`. On _arrt':':al at ~-~1e 1 ~abor~tory, the male rats wer.e 30 days old, the
`
`female rats were 37 days old, and the mice were all 30 days _ old.
`
`The animals were quarantined for an acclimation period (rats for
`s days, mice for .4·-:s days)', · ·assig'rl~d
`
`to ' '"control and · treated
`
`groups, and earmarked for individual identifi~ation.
`
`D. Animal }.laintenance
`
`All animals 1,1ere housed in temperature- and humidity-controlled
`
`4
`
`f
`
`I I
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