LEUKEMIA L-l2lO IN MECE. V. Abraham Goldin and John M. Venditti

65 Pages·2006·4.01 MB·English

EVALUATION OF ANTILEUKEMEC AGEMPS E@4PLOYINGADVANCED
LEUKEMIA L-l2lO IN MECE. V.
Abraham Goldin and John M. Venditti
(Laboratoryof Chemical Pharmacology,National Cancer Institute,
National Institutesof Health, Bethesda,?‘@ryland.)
Ira Kline
(MicrobiologicalAssociates, Inc., Bethesda, @ryland.)2i
INTRODUCTION
This report is our fifth of a series (4-7 ) presenting data obtained employing an
assay procedure for the quantitative eva.luation of the relative effectiveness of chemi
cal agents against systemic leukemia L-l2lO in mice. The assay procedure (1, 2) permits
the compounds to be rated with respect to their antileukemic specificityemploying
Amethopterinas a standard for therapeutic effectiveness.
In the current study, twenty-eight compounds not previously evaluated in this
series are rated according to their effectivenessin increasingthe survival time of
mice with systemic leukemia L@-l2lOon daily subcutaneous treatment. In addition,
thirty..four compounds previously reported in this series are re-evaluated in this assay
system (4-7). The current report also includes data relative to the influence of
factors such as the route of drug administration and the schedule of treatment on the
effectivenessof'selectedcompoundsof interest.
MATERIALS AND METHODS
The materials and methods, with certain minor modifications, are essentially the
sameas describedin previouspublicationsfranthis laboratory(l..9).
The experimentswere conducted in 20-30 gm., BDF1, CDBA, or D2BCW mice. The
strain, sex, and weight range of the mice used in each experiment, are reported in the
accanpanying tables.
Mice were inoculated subcutaneously in the right hind leg with 0.2 ml. of a
saline suspension of leukemia (L-l2lO) cells prepared from spleens of DBA/2 or CDRA
stock tumor mice. The level of the experimantal leukemic inocu.lum, for each experiment,
is reported in the tables. In additionto treated and controlmice that received the
experimental inoculum, each experinent included groups of untreated mice that received
serial dilutions of the experimental inocu.lum.
Treatment was initiated when the local tumor, at the site of inoculation, measured
7 to 12 mm. in diameter. In the current group of experiments, this was seven to nine
days following tumor implantation. For the individual experiments, the time of treat
ment initiation, noted in the tables, ranged from two to four and one half days prior
to the median day of death of the untreated controls. In each experiment, on the day
of treatment initiation, five or six mice selected at random from the population that
had received the experimental inoculumn were sacrificed, and. their spleens were implanted
subcutaneously into normal mice of the same strain. The consistent tumor death of the
recipients of spleen indicated that the disease was systemic when treatment was started.
The median survival tiu@s for the “retranspiant recipientsâ€(cid:157) are measured from the day on
which they were inoculated.
@JThisstudy was supportedby Contract No. SA-43-ph-2371from the Cancer Chemotherapy
National Service Center, National Cancer Institute, National Institutesof Health,
Public Health Service, U. S. Department of Health, Education, and Welfare.
.?JBDF1= (C57 BL/6 x DBA/2)F1
CDBA (BALD/c x DBA/2 )F1
D2BC = ( ZBC x DBA/2)F1
157
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158 CancerResearch Goldin andVenditti
Treatments were administered in the constant volume of 0.01 mi/gin of body
weight, and were generally continued, daily until death. In scene experiments, alterna
tive schedules of treatzr@nt were esnployed. Such instances are specifically noted in the
tables. Except where the intravenousor oral route is indicated,all drugs were in
jectedsubcutaneouslyin the scapulararea. Oraltreatmentswere by gavage. The method
employed for oral drug administration has been described previously in detail (9). Ex
perimentsinvolvingoral treatmentincludednormalmice which received the vehicle for
the test ccer@ouridby mouth.
Each compound studied, its source, its molecular formula,and the vehicle in
which it was administered is listed, in the tables.
The vehicle employed for each compound is coded as follows:
A distilled water
B 2 per cent sodiumbicarbonate solution
C 0.5 per cent methylcellulose
D 0.85 per cent saline solution
E dilute sodium hydroxide solution
F 5 per cent ethyl alcohol in n-saline
G phosphate buffer (pH 7.2)
The source of each compound is coded as follows:
1 Chemical-Biological Coordination 27 Dr. John R. Dice
Center Research laboratories
Nationa]. Academy of Science Parke, Davis and Company
National Research Council 2800 Plymouth Road
210]. Constitution Avenue Ann Arbor, Michigan
Washington 25, D. C.
35 Dr. Douglas A. Shepherd
4 Dr. A. H. Land Head, Biological Screening Offices
Technical Information Dept. The Upjohn Company
Merck, Sharp and Dobme Research Kalamazoo, Michigan
Laboratories
Rahway, New Jersey 37 Burroughs Wellcome and Company
1 Scarsdale Road
4P Merck and Company Tuckahoe 7, New York
Contract No. SA-43-ph-1948
to Cancer Chemotherapy National 43 Endocrinolo@rSection
Service Center Cancer ChemotherapyNational
Service Center
5 Dr. John A. Carbon National Institutes of Health
Organic Research Division Bethesda 14, Me.ryland
Abbott Laboratories
North Chicago, Illinois 49 Distillation Products Industries
Eastman Kodak Company
20 Southern Research Institute Rochester, New York
Birmingliern 5, Alabama
58A Professor Robert C. Elderfield
21F Dr. Anthony Schrecker Department of Chemistry
National Cancer Institute University of Michigan
Natlona]. Institutes of Health Ann Arbor, Michigan
Bethesda 14, Me.ryland
59E Dr. Charles Heidelberger
25 U. S. Army Chemical Warfare McArd.le Memorial laboratory
laboratories Medical School
Army Chemical Center, Me.ryland University of Wisconsin
@dison6, Wisconsin
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Goldin andVenditti CancerChemotherapy Screening Data 159
62A Professor Roland K. Robins 2l3A Dr. W. C. J. Ross
Department of Chemistry Chester Beatty Research Institute
Arizona State University The Royal Cancer Hospital
Tempe, Arizona Fulham Road
London, S. W. 3, England
67A The Givaudan Corporation
Delawanna, New Jersey 229A Dr. J. M. Ruegsegger
ClinicalResearch Section
74S Dr. Michael B. Shimkin Lederle LaboratoriesDivision
National Institutes of Health American Cyanamid Company
Bethesda 14, Maryland Pearl River, New York
99 The Minnesota Mining and Mfg. 233B Dr. S. S. Barkulis
Company Director of Microbiolo@rDivision
2301 Hudson Road Ciba Pharmaceutical,Inc.
St. Paul 6, Minnesota Summit, New Jersey
l4OF Dr. Jonathan L Hartwell 253 Mr. Frederic A. French
Cancer Chemotherapy National Mt. Zion Hospital
Service Center San Francisco 15, California
National Institutesof Health
285A Professor C. T. Babner
Bethesda 14, Maryland
Department of Chemistry
Carson- Newman College
201 ProfessorA. D. Welch
Jefferson City, Tennessee
Yale University
New Haven, Connecticut
365 The Lilly Research Laboratories
Eli Lilly and Company
210 Dr. Birth
Indianapolis 6, Indiana
Abteilung WME 3
FarbenfarbrikenBayer, A. G.
365A Dr. Koert Gerzon
Bayer Leverkusen
Organic ChemicalDivision
Verkauf Pharm C.
The Lilly Research laboratories
Leverkusen,Germany
Eli Lilly and Company
Indianapolis6, Indiana
In each experiment, the drugs were administered over a wide range of logarithmi
cal.l,yspaced dosage levels. For an active compound, as the dose level was increased,
there was an increase in the survival time of the mice. With further increase in
dosage, the toxicity of the drug for the host became limiting and this resulted in a
diminution of the survival time.
The optimal daily dose for a compound is defined as the dose level providing the
maximum median survival time. Where the maximum median survival time was observed at
more than one dose level, selection of the ciptimal dose is based on the entire individu
al survival time pattern. Instances in which the optimal dose may be outside the range
employed are noted in the tables by * or f. Where all dose levels produced toxicity,
denoted by *, the optimal dose may be lower than any used. Where no clear toxicity
appeared at any dose level employed, denoted by -f@,the optimal level may be higher than
any employed. In some cases, although the maxiimim median survival time occurred at one
of the extreme dose levels tested, the data indicated no advantage in testing at still
more extreme levels. Such instances are not noted specifica]..ly.
In each experiment, Amethopterin was employed as a standard. The compounds are
rated relative to the Amethopterin standard for efficacy in increasing the survival time
of the leukemic mice. The relative efficacy of a compound is computed in per cent as:
M
Mt c
x 100
M M
5 c
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160 CancerResearch Goldin and Venditti
Where Mt the median survival time at the optimal daily dose of the test compound,
M5 = the median survival time at the optimal daily dose of the Amethopterin
standard,
M the median survival time of untreated controls.
In studies of the influence of the route of drug administration or the schedule
of treatment on antileukemic effectiveness of the test compounds, two ratings are given.
In such cases, the compounds are rated (a) with respect -to subcutaneous, daily Aznetho
pterin employed as a standard, and (b ) with respect to the median survival time of the
- untreated controls. The latter rating is computed as Mt M
M
c
R@ULTS
The results of the current experiments are shown in Tables I through V. Table A
lists the compounds tested, the source of each, and the table in which the results ap
pear. ¶L@blVe presents detailed results of experiments involving the treatment of mice
with advanced leukemia. For each experiment, Table V shows the compounds tested, the
vehicle for each, and the dose levels employed. The route of drug administration and
schedule of treatment employed are also noted. In addition, Thble V shows, for each ex
perimental group, data on median and individual survival times and the number of sur
vivors, if any.
Thble I rates the compounds on daily subcutaneous administration relative to the
Amethopterin standard. Table I also presents summary results for each compound, and
shows the molecular formula for each, the optimal daily dose level, and the median sur
viva].time observed at this level. If no dose level employed produced an increase in
median survivaltime over that of the controls,no optimal daily dose is indicated in
Table I.
Table II summarizes the influence of the schedule of treatment on the anti
leukemic effectiveness of Nor-nitrogen Mustard, Epoxypropidine, Vincaleukoblastine, and
6-Azauracil. Thble III shows the infLuence of the route of administration on the rela
tive antileukeiniceffectivenessof folic acid congeners. Table IV summarizesthe in
fluenceof the route of administrationon the effectivenessof @b.@stargetnh,ree purmne
derivatives,and three glyoxalbisguanylhydrazones.
A. RElATIVE EFFECTIVEN@SOF COMPOUNDOSNDAILYSUBCUTANEOUTSREkTMENT
1. Alky].atirig Agents (Thble I Section 1 Th.ble V Experiments DL-l24 l28@
135 138 141 144 145 147 149 152 153 157 158 l6l@ and 163):
a. F@thyleneimines
MEPA, OPSPA, Thio-TEPA, TEM, and TEPA exhibited appreciable antileukemic
activity ranging fran 34 to 52 per cent of the Amethopterin effect. These data are in
agreement with our previous observation (4) that the effects of the thiophosphoramides
(Thio-TEPA; OPSPA) against advanced leukemia L-12l0 are comparable to those of the
correspondingphosphoramides (TEPA;MEPA).
The observation that cr-Vinyl-l-aziridineethanol(NSC#45726) was active
(40-43 per cent of the activity of Amethopterin) against systemic leukemia L-l2lO while
@-Vmny1-l-aziridineethano(lNSC#45725)was relativelyinactivehas been previously re
ported by us elsewhere (8). It was suggested (8) that the antileu.kemic activity of
NSC#26806 (Tetramin),which is a mixture of these primaryand secondaryalcohols, was
due to the a-Vinyl-l-aziridineethanol (NSC #45726) component. The detailed data of the
previouslyreportedexperiments(8)are containedin the currentreport (TableV, Exps.
DL-141, 144, and 152).
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Goldin and Venditti Cancer Chemotherapy Screening Data 161
b. Nitrogen tvtistards
The 6-methyl derivative of Uracil Mustard (DOPAN) exhibited no advantage over
Uracil Mustard in this assay system ([email protected]).
Comparison of the optimal daily doses for I4istargen (1.80 and 3.00 mg/kg) and
Nor-nitrogen Mustard (108 mg/kg) indicates that for equal dose Nor-nitrogen Mustard is
considerably less effective and less toxic than Mastargen. When compared in the same
experiment, however, nor nitrogen mustard exhibited a slightly greater antileukemic
effectiveness than Mustargen at optimal levels of treatment (Exp. DL-l38).
C. Epoxides and Methanesu.lfonates
Epoxypropidine, as previously reported in this series (6) again produced an
antileukemic effect of 19 per cent relative to I@methopterin. The methanesulfonates
tested were inactive in the current experiment.
2. Purine Derivatives (Table I Section 2 Table V Experiments DL-lll
139 and 151):
6-Mercaptopu.rine was the most active purine studied in these current experi
ments. As previously described (5,6), 6-tvlPwas more effective and less toxic when
dissolved in dilute sodium hydroxide than when suspended in methylceliulose (Exp.
DL-l39). Of the other purines tested, 6-Thioguanine showed the greatest activity (39
per cent).
3. Pyrimidines (Table I Section 3 @bleV Experiments DL-120 and 122):
Dicb.loro-Daraprimshowed an effectiveness of 19 per cent relative to Arnetho
pterin. The data indicate, however, that drug toxicity was occasioned over the entire
dose range employed (Exp. DL-l20). It is possible that Dichioro-Daraprim might have
been more effective at lower daily dosage levels. 6-Azauracil was inactive (Exp.
DL-l22). Mice receiving up to 1667 mg/kg/day of 6-Azauracil exhibited no evidence of
drug toxicity or local tumor inhibition.
4. Steroids and Dietbylstilbestrol (Table I Section 4 Table V Experi
ments DL-145 150 151 and 154):
Prednisone was 16 per cent as effective as Ainethopterin. The other steroids
were relatively inactive. None of the steroids tested or Diethylstilbestrol elicited
body weight loss over the dose range employed.
5. Glyoxalbisguanylhyd.razones (Table I Section 5 Table V Experiments
DL-l20 133 and 160):
The high degree of antileukemic activity of the methyl derivatives of Gly
oxalbisguanylhydrazone and the inactivity of Glyoxalbisguanylhydrazone itself, pre
viously reported in this series (5, 6) were confirmed in the current experiments.
6. Colchicine Derivatives (Table I Section 6 Table V Experiment DL-l5l):
Colchinol and N-Acetyl colchinol were inactive at the doses employed in this
experiment(Exp.DL-151).
7. Qp.inolineDerivatives(TableI Section7 Table V ExperimentDL-149):
None of the quinolinederivativestesteddemonstratedappreciableactivity.
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162 CancerResearch Goldin and Venditti
8. PodophyflotoxinDerivatives (TableI Section 8 Table V Experiment
DL-142):
The isopropylamine salt of Podophyllotoxin, Hydrogen glutarate, was II
per cent as active as Arnethopterin. Podophyllotoxin chloroacetate-a>.pyridinium chloride
and Podophyllotoxin itself showed little or no activity.
9. FolicacidDerivatives(TableI Section9 Table V ExperimentsDL-l24
and 125):
The current report shows the detailed data of previously published obser
vations that brcanination or chlorination in the benzene ring of Ainethopterin results in
compounds with greatly enhanced antileukemic activity on subcutaneous administration
(7,9).
10. Other Cc*npounds (Table I Section 10 Table V Experiments DL-125 129
135 144 145 146 160 and 163):
2-F@thylamino-1,3,4-thiadiazole was 50 per cent as effective as Ainethopterin
(i@cp. DL-l44). In two experiments (DL-l63, 135), l-Methyl-l-nitroso urea was 37 and 16
per cent as effective as Amethopterin. None of the remaining compounds elicited a rela
tive effectiveness of more than 20 per cent.
B. INFUJ@CE OF THESCHEDULEOF ThEATM@TONAMTILEUKFMLCEFFECTIVENESS
(Table II and Table V Experiments DL-l22 129 135 and 144)
Table II summarizes the influence of treatment schedule on antileukemic activity
of Nor-nitrogen Mustard, E@poxypropidine, Vincaleukoblastine, and 6-Azauracil. The de
tailed data of the experiments is shown in Table V. In Table II, the compounds are
rated relative to Amethopteringiven daily.
The antileukemic effectiveness of Nor-nitrogen Mustard, Epoxypropidine, or Vinca
leukoblastine was not markedly increased by increasing the interval between treatments.
6-Azauracil, which was inactive and nontoxic on daily administration, produced only a
one clay increase in median survival time when given four times per day at a dose of 216
mg/kg. On this schedule, however, weight loss was observed at a dose of 1000 mg/kg
(total dose, 4000 mg/kg/day).
C. INFLUENCEOF THEROUTEOFADMENISTRATIONONTHEANTILEUKEMEC
EF@CTIVEN@ZSOF FOLIC ACID CONGENERS
(Table III and Thble V Experiments DL-124 and DL-125)
The diminution in the effectiveness of both 3',5'-Dichioroamethopterin and
Ainethopterin on oral administration has been previously reported from this laboratory
(9). The current data confirms this observation, and in addition shows that 3'-Bromo
5'-chloroaznethopterin and 3'-Bromoaznethopterin similarly exhibit decreased activities
via the oral route.
D. INFLUENCEOF THEROUFEOFADMENISTRATIONONTHEANTILEUKEMIC
EECTIVENEES OF OTHERCOMPOUNDS
(Table IV and Table V Experiments DL-111 120 128 and 133)
Table IV summarizesdata comparingthe activitiesof seven compoundsemploying
various routes of administration. The detailed data are shown in Table V.
Z4istargenwas no more effectivewhen given intravenouslythan when given subcu
taneously (Exp.DL-128).
The activities of 6-Mercaptopurine,6-Thioguanine,and 2-Aznino-6-(l-methyl-4-
nitro-5-imidazo].ylthio)-purmnweere compared on oral and subcutaneousadministration
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Goldin and Venditti Cancer Chemotherapy Screening Data 163
(&p. DL-lll). All three displayed similar activities via either route of adminis
tration although in each case more drug was required orally to give an effect comparable
to that observed on subcutaneous injection.
Both of the methyl derivatives of Glyoxalbisguanyihydrazone were slightly more
active subcutaneously than orally. Of interest is the observationthat Glyoxalbis
guanyihydrazone, inactive when given subcutaneously, displayed some activity when given
orally (Exps. DL-l20 and 133).
REFERENCES
1. Goldin, A., Venditti, J. M., Humphreys, S. B., and Mantel, N. ?vbdification of
Treatment Schedules in the Management of Advanced Muse Leukemia with Amethopterin.
J. Nat. Cancer Inst. @7:2O3-2l2, 1956.
2. _______________________________. Quantitative Evaluation of Chemotherapeutic
Agents Against Advanced Leukemia in Mice. J. Nat. Cancer Inst. @j:495-5ll, 1958.
3. Goldin, A., Venditti, J. M., Humphreys , S. R., Shuster, L., Darrow, R. A., and
Mantel, N. Advanced Leukemia as a Tool for Chemotherapeutic Studies. Acta Unio
Internat. Contra Cancrum @:642-65O, 1960.
4. 001dm, A. , Venditti, J. M., Kline, I. , and Mantel, N. Evaluation of Antileukemic
Agents E@rrploying Advanced Leukemia L-l2lO in Mice. In “Cancer Chemotherapy Screen
ing Data IVâ(€(cid:157)J. Leiter, ed.) Cancer Research @:429-466,1959.
5. _______________________________. Evaluation of Antileukemic Agents Baploying
Advanced Leukemia L-l2lO in Mice II. In “CanceCrhemotherapyScreeningData VIâ€(cid:157)
(J. Leiter, ed.) Cancer Research @Q:382-448,1960.
6. ________________________________. Evaluation of Antileukemic Agents @nploying
Advanced Leukemia L-l2lO in Mice IV. In “CanceCrhemotherapyScreeningData IXâ€(cid:157)
(J. Leiter, ed.) Cancer Research @:27-92,1961.
7. Venditti, J. M., Humphreys, S. R., Mantel, N., Kline, I., and Goldin, A. Evalu
ation of Antileukemic Agents Fknploying Advanced Leukemia L-l2lO in Mice III. Conge
ners of FolicAcid. In “CanceCrhemotherapyScreeningData VIIIâ(€(cid:157)J. Leiter, ed.)
Cancer Research @Q:698-733, 1960.
8. Venditti, 3. M., Goldin, A., and Kline, I. Comparison of the Effectivenessof
Tetramin and Its Components Against Advanced Leukemia L-l2lO in Mice. In Cancer
Chemotherapy Reports No. @j:73-76, 1961.
9. Venditti, J. M., Schrecker, A. W., Mead, J. A. R., Kline, I., and Goldin, A. In
fluence of the Route of Administration on the Relative Effectiveness of 3,, 5' -Di
chloroamethopterin and Amethopterin Against Advanced Leukemia (L-l2lO) in Mice.
Cancer Research @Q:l45l-1456, 1960.
ACKNOWLEDGEMENTS
The authors wish to thank Dr. Charles G. Zubrod, Dr. G. Burroughs Mider, Dr. Carl
G. Baker, Dr. Kenneth M. Endicott, Dr. l4irray J. Shear, Professor E. K. Marshall, Jr.,
Dr. Stuart M. Sessans, Dr. Joseph Leiter, Dr. Robert D. Coghill, Mr. George A. Brandner,
Dr. I@ward Bond, Dr. Ronald B. Ross, Dr. Erwin P. Voilmer, and Dr. Saul Schepartz for
their interest in this program.
We are grateful to Dr. Anthony W. Scbrecker, Dr. J. A. R. Mead, Dr. Michael A.
Chirigos, Mr. Stewart R. Hunxphreys, Dr. John P. Glynn, and Mr. Leonard D. Mitchell for
their helpful suggestions, and to Naomi T. FitzGibbon, Dorothy A. Osborne, Sam C.
Mangano, James J. Mrse, and Miriam Gang for their help in the preparation of the manu
script and tables.
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164 CancerResearch Goldin and Venditti
It is a pleasure to acknowledge the valuable assistance of E. Waynn Artis and the
following in the execution of these experiments:
Haywood Waters Melissa Washington
Dunlap Scott, Jr. Wilma Todd
Carroll L. Jackrnon Dacota Jordan
Lenwood Keys James Keys
Georgiana Sanders John Davis
David Gordon Robert Wheeler
lymond Williams James Mcllwain
flnmaMcCullough Edward Stephens
Philip Freedenberg
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Goldin and Venditti Cancer Chemotherapy Screening Data 165
TABLEA
LISTOF CO@OUNDS
NU@3OURCI—————No.IIIIIIIVV
ENTRYNSC No.COMPOUND NAI€TABLE
27558 74&:/ Amethopterin 229A x x x x x
27559 745 Bis(1-aziridinyl )morpholino-phosphine oxide
(MEEA) 229A x x
27560 750 Methanesulfonic acid, tetramethylene ester
(?,@rleran) 37 x x
27561 752 6-Purinethio]., 2-amino- (6-Thioguanine) 37 x x x
27562 755 6-Purinethiol,hydrate (6-Mercaptopurine
hydrate) 37 x x x
27563 762 Diethy].amine, 2,2'-dich].oro-N-metby].
(wistargen) 4 x x x
27564 305]. N-Metby].formamide 49 x x
27565 3052 Methanesulfonic acid, nonamethylene ester
(Nonane) 49 x x
27566 3062 Pyrimidine,2,4-diaznino-5-(3',4'-dickloro
phenyl)-6-ethyl- (DichJ.oro-Daraprlm) 37 x x
27567 3070 4,4'-Stilbenediol,a,a'-dietbyl
(Dietbyistilbestrol) 43 x x
27568 3425 as-Triazine-3,5(2E,4E)-dlone (6-Azauracil) 201 x x x
27569 4238 2- (@-Dimethy1aminostyry1)-].-methy1quino1inium
iodide 285& x x
27570 4239 4-(@-Dimethy].aminostyry].)-1-methy1quino1inium
iodide 285A x x
27571 4730 ].,3,4-Thiadiazo].e,2-etby].amino- 229A x x
27572 6396 Trls(].-aziridinyl)phosphine sulfide
(Thio-T@A) 229A x x
27573 9703 17, 21-Dihyd.roxy-pregn-4-ene-3,].]., 20-trione
(Cortisone) 43 x x
27574 9705 U@, 21-Dihydroxypregn-4-ene-3, 20-dione
(Corticosterone) 43 x x
27575 9706 2,4,6-Tris(1-azfridixyl)-s-triazine (TEM) 229A x x
27576 9717 Tris(l-aziridiny].)-phoaphine oxide (TEPA) 1 x x
27577 9894 4,4'- (1, 2-Diethyletbylene)-diphenyl
(Rexestrol) 43 x x
27578 10023 Pregna-1, 4-diene-3,11,20-trione,17, 2].-
dibydroxy- (Prednisone) 43 x x
@:N/ SCNo.740Is used as a standard. The test compounds are rated relative to NSCNo. 740
In TablesI-IV.
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166 Cancer Research Goldin and Vendirxi
TABlEA - (Continued)
LIST OF COMPOUNDS
NU@ER—
@2RY No.C@OTR1D NAI.@TABLE
No.NSC
I— IIIII— IV—V
27579 10429 Bis(l-aziridiny].)ixrpholino-pbosphine sulfide
(oPsPA) 59E x x
27580 10482 @.dnoline,4(-p@-dimetbyl)-aminoatyryl-,
dihydrochioride 285A x x
27581 10483 ].l@,].7,2].-Prihydroxy-pregn-4-ene-3, 20 dione
(Cortisol) 43 x x
27582 10873 Diethy].amine,2, 2'-dichloro-, hydrochlorIde
(Nor-Nitrogen titistard) 27 x x x
27583 11318 @x-fluorocortIsol 43 x x
27584 3.2198 Testosterone, 4,5cx-dlhydro-Scz-metby].-,
propionate 43 x x
27585 14575 9H-Purlne-6-thiol,9-etby]. 20 x x
27586 15186 @z-fluorocortisol,2l-acetate 4 x x
27587 17261 2,5.-Bis(l-azIrldinyl)-3, 6-diprcpoxy-@-
benzoquinone (E-39) 210 x x
27588 18016 Metbanesu.1.fonic acid, 2-chloroetbyl ester 213A x x
27569 18271 Propionamide,N,N'-/@, 6-bia(l-aziridix@].-p-
benzoquinon-2,5-ylene@7bIs- 233B x x
27590 18439 Anhline,N,N-bia(2-chloroetbyl)-2,3-di
n@thoxy- 5 x x
27591 19487 9li-Purine-6-thiol,9-cyc].c@entyl- 20 x x
27592 19488 9E-Purine-.6-thiol,9-butyl- 20 x x
27593 22183 G].yoxa].bisguanylbydrazone n@noau].f@te
pentahydrate 253 x x x
27594 22185 Methylg]yoxalbisguat@r].bydrazone [email protected]
n@nohydrate 253 x x x
27595 23436 2,4-Bis(l-aziridinyl)-6-methyl-5-nitro
pyrimidine 58A x x
27596 23891 2-@is(2-cb].oroethyl)amincmethylJbenz
imidazo].e,hydrochloride 67A x x
27597 23909 Urea,l-methyl-l-nitroso- 20 x x
27598 24818 POdOphy].lOtOXin 217 x x
27599 26805 Methanesu].fonic acid, ethyl ester 42 x x
27600 26806 l-Aziridineetbanol,cz-vinyl-nhixture with
@-vinyl-l-aziridineetbanol (Tetra@in
mixed isomers) 4P x x
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