(CANCERRESEARCH40, 1921-1 927, June1980]
0008-5472/80/0040-0000$02.00
Distributionof N-NitrosomethylbenzylamineEvaluatedby Whole-Body
Radioautographyand Densitometry1
Patricia L. Kraft2 and Steven R. Tannenbaum3
Department of Nutrition and Food Science, Massachusetts Institute of Technology. Cambridge. Massachusetts 02139
ABSTRACT
The distribution of N-nitrosomethylbenzylamine (MBN) was
studied using whole-body radioautography and densitometry.
Male Sprague-Dawley rats were given N-nitroso-[methyl-'4C1benzylamine ([methyl-'4C]MBN) (3.3 mg, 1 mCi/kg body
weight i.p.) or N-nitrosomethyl[benzyl-7-'4C]amine (2.1 mg, 1
mCi/kg body weight i.p.), and sagittal sections were taken at
15 mm, 60 mm, 3.5 hr, 7.25 hr, 24 hr, and 3 days after
injection.
Very high levels of [methy!-14C@MBN-derivedradioactivity
were present at all time periods (15 mm to 3 days) in the three
target tissues for MBN-induced tumorigenesis (nasal cavity,
lung, and esophagus). The liver contained high and the kidney
contained moderately high levels of radioactivity at all time
periods. A considerable amount of radiolabel was present in a
number of tissues at 24 hr. After 3 days, very high levels were
observed only in the tissues in which MBN-induced tumors
eventually developed.
Following administration of N-nitrosomethyl[benzyl-7-14CJ
amine, levels of radioactivity in most tissues were lower than
following injection of [methy!-'4C]MBN; however, very high
levels were present in the nasal cavity, liver, and kidney.
Considerably less radiolabel remained at 24 hr and 3 days
following injection of N-nitrosomethyl[benzyl-7-'4C]amine than
following [methyl-14C]MBN administration. At 24 hr, benzyl
moiety-derived radiolabel was present in either the enterohe
patic circulation or the tissues in which MBN-induced tumors
arose. At 3 days, the highest level of radioactivity was con
tamed by the liver, although detectable levels remained in the
nasal cavity and lung, two tissues in which MBN induced
carcinomas.
The findings of this study indicate that the carcinogenicity of
MBN may be the result of the inability of the target organs
(esophagus, nasal cavity, and Iungs)to readily clear methylated
macromolecules, benzylated macromolecules, or the oxidized
metabolites which arise during nitrosamine metabolism.
INTRODUCTION
MBN4is an unsymmetricallysubstitutednitrosaminewhichis
mutagenic (13, 19, 21—24),toxic (5, 9), and carcinogenic (1,
5, 6, 14, 17). The compound has been shown to selectively
induce esophageal tumors in rats (5), and the 2 a-acetoxy
, This work was supported in part by Research Grant 2-POl -ES00597 from
the National Institute of Environmental Health Sciences, NIH.
2 Recipient
of a National
Research
Service
Award
1 -T32-ES-07020
from
the
National Institute of Environmental Health Sciences, NIH.
3 To whom requests
for reprints
4 The
used
abbreviations
are:
should be addressed.
MBN,
N-nltrosomethylbenzylamine;
DMN,
derivatives of MBN display striking differences in mutagenicity
(19). Of interest because of its structure, toxicity, organ-spe
cific carcinogenicity, and mutagenicity of oxidized derivatives,
we undertook an extensive investigation of MBN which encom
passed toxicity and carcinogenicity testing, pharmacokinetic
and metabolic studies, and tissue distribution and persistence
evaluations. The latter topic is the focus of the present report.
Whole-body radioautography was performed at 6 time points
after injection of [14CJMBN.The 4 earlier time points were
chosen to reflect tissue distribution and uptake. Tissue per
sistence of radiolabel was determined at the 2 later time pe
nods. Densitometric analysis of the radioautograms permitted
the calculation of half-lives of dpm equivalents in selected
tissues. Whole-body radioautography has recently been used
to investigate the distribution of DMN and MBN (9, 10). In the
latter study, a dose of N-methyl[U-3H]-N-nitrosobenzylamine
producing acute toxicity (100 mg, 10 mCi/kg body weight i.v.)
was administered to male Donryu rats. In the present study, a
fraction of the 50% lethal dose of MBN was administered to
male Sprague-Dawley rats, and the use of [14C]MBN circum
vented the problem of loss of tritium due to hydrogen exchange
and metabolism of the nitrosamine.
MATERIALS AND METHODS
Animals and Diet. Male Sprague-Dawley rats (Charles River
Breeding Laboratories, North Wilmington, Mass.) weighing 120
to 160 g were permitted food (Charles River Rat/Mouse/
Hamster Formula, Country Foods, Syracuse, N. Y.) and tap
water ad libitum. The animals were housed in fume hoods in
plastic tubs 13 x 11 x 5 inches (Superior Chemical Company,
Somerville, Mass.) containing Ab-Sorb-Dri bedding.
Chemicals. [methyl-14C]MBN(specificactivity,6 mCi/mmol)
and [benzyl-7-14C]MBN (specific activity, 5 mCi/mmol) were
synthesized by Paul L. Skipper (15). The radiochemical purity
of both compounds, determined by thin-layer chromatography
on silica gel using acetone, was greater than 99%.
Whole-Body Radioautography. Twelve rats were given i.p.
injections of [methyl-14C]MBN(3.3 mg, 1 mCi/kg body weight)
or [benzyl-7-14C]MBN (2.1 mg, 1 mCi/kg body weight) and
then frozen by immersion in a bath of dry ice and hexane at 6
intervals postinjection: 15 mm, 60 mm, 3.5 hr, 7.25 hr, 24 hr,
and 3 days (1 rat/time period for each of the 2 compounds).
The 4 earlier time points were selected based on whole-blood
clearance of MBN. In approximately 10 mm, 10% of an i.p.
dose of MBN was cleared from whole blood. Fifty % was
cleared in 65 mm, 90% in 21 7 mm, and 99% in 434 mm.5
Following immersion in dry ice-hexane, the animals were
embedded in a mold containing methylcellulose which was
di
methylnitrosamine; [methyl-'4C)MBN, N-nitroso(methyl-'4C]benzylamine; [benzyl
7-'4CJMBN,
N-nlfrosomethyl(benzyl-7-'4Cjamine.
Received August 31 1979; accepted February 28, 1980.
JUNE1980
5 P.
L.
Kraft,
P.
L.
Skipper,
and
S.
R.
Tannenbaum.
Pharmacokinetics
and
metabolism of N-nitrosomethylbenzylamine, submitted for publication.
1921
Downloaded from cancerres.aacrjournals.org on June 18, 2017. © 1980 American Association for Cancer Research.
P. L. Kraft and S. R. Tannenbaum
placed in a —
25°freezer until frozen. The frozen methylcellu
lose block was mounted on the stage of a Jung microtome
(Kenneth A. Dawson, Inc., Belmont, Mass.) housed in a Harris
cryostat (Harris Manufacturing Company, Cambridge, Mass.).
Sagittal selections (60 sm thick), 60 to 80 at the first 4 time
points and 30 to 40 at the latter 2 intervals, were picked up on
Scotch 810 transparent tape (L. E. Muran, Boston, Mass.),
transferred over dry ice, and stored in a low-humidity cold
room (—20°)
until excess tissue moisture was removed. In a
photographic darkroom at room temperature, the whole-body
sections and a series of 7 filter paper discs (Whatman No. 52;
Fisher Scientific Company, Medford, Mass.) containing known
amounts of radioactivity (dpm = 81 , 143, 243, 538, 905,
1619, 3344 ±10% or dpm = 137, 215, 421, 758, 1458,
2965, 551 2 ±10%) were taped to Kodak No-Screen Medical
X-ray film (E. M. Parker, Brookline, Mass.). The films were
clamped between aluminum sheets and exposed at room tem
perature. Film exposure resulting from the standardized discs
provided a scale for evaluating densities in the whole-body
section radioautogram. After suitable exposure, sections were
removed, and the X-ray films were processed in Kodak X-ray
developer and fixer (E. M. Parker). Exposure ranged from 2 to
6 weeks, depending upon the densitometric quality of the
radioautograms.
Densitometry. Radioautographicdensities of the standard
spots and selected tissues (the nasal cavity, the blood con
tamed within the heart, the liver, and the musculature) were
determined using a Macbeth densitometer, Model TD-502 LB
(Macbeth Instrument Company, Newburgh, N. Y.). A linear
standard curve relating the dpm equivalents ofthe standardized
discs and the corresponding densitometer readings enabled
the calculation of dpm equivalents of tissues, including those
lighter or darker than the standards, based on densitometer
readings. Densitometric analysis required an area of uniformly
darkened film 1 mm in diameter which precluded examination
of a number of tissues including the esophagus, lung, and
regions of the kidney at certain time points.
Whole-Body Radioautography. Semiquantitative data for
the distribution of radioactivity following injection of [methyl
‘4C]MBN
and [benzyl-7-'4C]MBN is presented in Tables 1 and
2, respectively. Tissues were assigned values from 1 to 10
based on the darkening of the X-ray film. Numbers were
designated on the basis of dpm equivalents, determined by
densitometry and by visual comparison to the 7 standard spots.
Several tissues were either lighter or darker than were the
standard discs which required expansion of the scale from 1 to
7 to 1 to 10. Radioautographs are shown in Figs. 1 to 3.
Following [methyl-14C]MBN administration, very high levels
of radioactivity were present at all time points in the 3 tissues
in which tumors developed following i.p. administration of MBN
(nasal cavity, lung, and esophagus6). Radioactivity distribution
was not uniform throughout the lung; areas of radiolabel con
centration were observed at all time periods. Label localization
also occurred in the salivary glands at 3 days. The liver con
tamed high and the kidney moderately high levels of radioac
6 P. L. Kraft,
J. C. Murphy,
and
S. R. Tannenbaum.
Toxicity
of N-nitrosomethylbenzylamine, submitted for publication.
1922
Dawleyratsfollowingadministrationof(methyl@14CjMBNarague
densitybRegionof
Film
15
mm
60
mm
3.5
hr
7.25
hr
24
hr3
8, 10
10
10
10
106,
0CBlood pharynx, trachea,
esophagus (epithelia)6,
6
8
10
10
10
32Lungin heart
4
5
5
4
Localization
4Thymus
Background
10
6
10
6
10
6
10
6
6
6
corresponding film
daysNasal
cavity
10Tongue,
84Uver (cortex)
85Kidney
6
7
9
8
Cortex
Corticomedulla
64Urinary
Medulla
6
7
6
7
6
4
5
10Stomach
tract (contents)
Fore- and glandular junction
(epithellum)
Fore- (epithelium)
Glandular
Epithellum
7Esophageal
Secretory
10
610
7
10
6
entry into stomach
(epithelium)9Small
8
10
10
10
5
6
7
8
10
10
5
106
8
10
10
10
7
5
5
8
7
6, 8
intestine, colon
Epithelium
Proximal contents
73-4Spleen
Distal contents
8Salivary
(red pulp)
5
6
8
8
@Musculature
5
6
6
6
67d
3
5
5
4
33
glands
1
4
: Dosewas3.3mg,1mCi/kgbodyweighti.p.
RESULTS
@
Table 1
Film densities of whole-body radioautographs prepared from male Sp
and
carcinogenicity
Numbers assigned based on densitometer readings and visual comparison:
0, film background; 1, film slightly exposed; 10, film blackened.
Esophageal epithelium.
Level for regions of radiolabel concentration within the salivary gland.
tivity at all time periods. The radioactivity distribution pattern of
the liver at 24 hr and 3 days indicated that intestinal radiolabel
entered the enterohepatic circulation. A considerable amount
of radioactivity was present in a number of tissues at 24 hr: the
esophagus, nose, and lung, as well as the thymus, liver, kidney,
salivary glands, and epithelium of the gastrointestinal tract. By
3 days, very high levels were observed only in tissues in which
MBM-induced tumors ultimately arose.
In general, tissue levels of radioactivity following injection of
[benzyl-7-'4C]MBN were lower than following administration of
[methyl-'4C]MBN. Notable exceptions were the nasal cavity,
liver, and kidney. The nasal cavity contained very high levels
of [benzyl-7-14C]MBN-derived radioactivity at the 4 earlier time
points. Very high levels of radiolabel were present in the kidney
and urinary tract or bladder at 15 and 60 mm. Radioactivity
uptake by the tongue, pharynx, trachea, and esophageal epi
thelium was much less pronounced than that observed with
[methyl-'4C]MBN and had only begun to exceed tissue (tongue)
CANCERRESEARCHVOL. 40
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Tissue Distribution of[14CJMBN
Table2
5
Film densities of whole-body radioautographs prepared from male Sp
D8.wleyrats following administration of(benzyl@7@14CJMBNarague
density@'Reglonof
Film
U,
0
z
daysNasalcavity
corresponding film
15
mm
60
mm
3.5
hr
7.25
hr
31Tongue
10
10
9
6,10
1Tongue,
4
5
pharynx, trachea,
(epithelium)0Bloodinheart
esophagus
5
24
hr3
C,,
0
I
10
I—
U,
I-
5—6 1-2
3
2
z
w
-J
>
20Lung
6
6
3
3
Localization
1Uver
Background
6
6
6
4
5
4
43Kidney
7
9
6
5
Cortex
Corticomedulla
10Urinary
Medulla
7
8
3
22
F
I
4
2
2
2
1
9
10Esophageal
tract (contents)
10
entry Into stomach
(epithellum)Small
1
1
234567
TIME IN HR
Chart 1. Tissue dpm equivalents obtained from whole-body radioautographs
of male Sprague-Dawley rats given injections of [benzyl-7-'4C)MBN (2. 1 mg, 1
mci/kg body weight i.p.). Radioautographic densities produced by selected
tissues and standard spots were compared using a densitometer. Tissue levels
were expressed as dpm equivalents (thousands). 0, nasal cavity; A. kidney
(medulla); x , liver; & kidney (cortex); •,
heart (blood); 0, musculature.
Intestine,colon
Epithelium
Proximalcontents
3Spleen
Distal contents
.
10
10
8
3
— 22
U,
0
6
z
< 20
U,
0
1Salivaryglands
(red pulp)
3
2
2Musculature
5
6
3
4
5
1
I
2
U,
I-
z
a Dose was 2.1 mg, 1 mCi/kg body weight i.p.
b
Numbers
assigned
based
on
densitometer
readings
LU
and
visual
comparison:
0, film background; 1•
film slightly exposed; 10, film blackened.
-J
>
0
background at 3.5 hr. Areas of radiolabel localization also
occurred in the lung following [benzyl-7-'4CJMBN injection, but
only from 3.5 hr onward. The distribution of radioactivity in the
liver at 3.5 hr and beyond indicated that [benzy!-7-'4C]MBN
derived radioactivity also entered the enterohepatic circulation.
Considerably less radioactivity persisted (present at 24 hr and
3 days) following administration of [benzyl-7-14C]MBN than
following injection of [methy!-14CJMBN.At 3 days, the highest
level of radioactivity was contained by the liver. Barely detect
able levels remained in the nasal cavity and lung.
Densitometry. Tissue dpm equivalents rose and fell more
sharply following injection of [benzyl-7-'4C]MBN (Chart 1) than
following administration of [methyl-'4CJMBN (Chart 2). Follow
ing administration of [methy!-14CJMBN,peak dpm equivalents
were observedat 60 mm in the blood (in the heart) and at 3.5
hr in the nasal cavity and liver. Musculature dpm equivalents
probably reached a peak between 60 mm and 3.5 hr (Chart 2).
In contrast, following [benzy!-7-'4C]MBN injection, peak dpm
equivalents were observed at 60 mm in all 4 tissues analyzed
(Chart 1).
Equations for clearance of dpm equivalents could only be
calculated using data at time points at and after the observed
peak, namely, 3.5, 7.25, and 24 hr for [methyl-'4C]MBN, and
60 mm, 3.5 hr, and 7.25 hr for [benzyl-7-'4C]MBN. Clearance
equations calculated for [benzyl-7-'4C]MBN using data at 3.5,
JUNE1980
LU
0@
0
I
234567
TIME
IN HR
Chart 2. Tissue dpm equivalents obtained from whole-body radioautographs
of male Sprague-Dawley rats given injections of (methyl-'4CJMBN (3.3 mg, 1
mCi/kg body weight i.p.). Radioautographic densities produced by selected
tissues and standard spots were compared using a densitometer. Tissue levels
were expressed as dpm equivalents (thousands). 0, nasal cavity; x , liver; A,
kidney (medulla): •.
heart (blood); £3,
musculature.
7.25, and 24 hr had poorer correlation coefficients. Estimated
tissue half-lives of 14Cequivalents were calculated from clear
ance equation rate constants. The 14C equivalent half-lives
were considerably
shorter following administration
of [benzyl
7-'4C]MBN than following injection of [methy!-14C]MBN: 2 to 4
hr versus 18 to 34 hr, respectively (Tables 3 and 4). For a
given tissue, there was favorable agreement between the clear
ance equation intercepts calculated for methyl and benzyl dpm
equivalents. For example, intercepts for nasal cavity clearance
equations were 9.9 and 9.8.
DISCUSSION
Whole-body radioautography was utilized to demonstrate the
1923
Downloaded from cancerres.aacrjournals.org on June 18, 2017. © 1980 American Association for Cancer Research.
P. L. Kraft and S. R. Tannenbaum
Table 3
Equations for clearance of dpm equivalents from selected tissues following
administration of(benzyl- 7@4CjMBNato male
ratsHalf-life
Sprague-Dawley
(r)Nasal
Tissue
Clearance equation
cavity
Blood (heart)
Liver
Musculature
—0.98a
In dpm
In dpm
In dpm
In dpm
=
=
=
=
9.8
7.7
8.4
7.0
Correlation
coefficient
(hr)
—O.17t
—O.35t
—O.19t
—O.35t
4
2
4
2
—0.68
—0.98
—0.99
0
0
Table 4
Equations for clearance of dpm equivalents from selected tissues following
administration of(methyl@14CJMBNa
to maleratsHalf-life
Sprague-Dawley
CorrelationTissue
(r)Nasal
Clearance equation
(hi)
—0.81Blood
cavity
In dpm
—0.99Liver
(heart)
In dpm
—0.95MusculatureIn dpm
—0.93a
In dpm
21
18
34
22
Dose
was
3.3
mg,
9.9
7.1
8.4
7.0
1 mCi/kg
weight
coefficient
‘
z
LU
C)
z
C)
:D
x
4
p.
tissue distribution, uptake, and persistence of [‘4C]MBN.
As
shown in the radioautographs at 24 hr (Figs. 1c and 2c), both
methyl and benzyl moiety-derived radiolabel were present in
the nasal cavity, lung, and esophagus, the 3 tissues in which
MBN-induced tumors arose.6 lizuka et a!. (9) also reported that
considerable radioactivity remained in the esophagus at 24 hr
following a lethal dose of MBN. After 3 days, all 3 target tissues
contained very high levels of [methyl-14C]MBN derived radio
activity, but detectable amounts of [benzyl-7-'4C]MBN-derived
radiolabel remained in only the nasal cavity and lung (the 2
tissues in which carcinomas developed). At both 24 hr and 3
days, there was more methyl label than benzyl label.
The dpm equivalents of selected tissues were determined by
comparing densitometer readings of regions of X-ray film cor
responding to tissues and standard discs. In the nasal cavity,
liver, and musculature, methyl and benzyl dpm equivalents
peaked at 3.5 hr and 60 mm, respectively. Methyl dpm equiv
alents remained in these tissues approximately 10 times longer
than did benzyl dpm equivalents. The methyl moiety may have
been incorporated into blood and tissue constituents via normal
biosynthetic pathways (6). Following iv. injection of mice with
[14C]DMNand [‘4C]formaldehyde,
considerable amounts of ra
dioactivity were taken up by tissues with high rates or protein
synthesis or cell turnover, including the epithelia of the nasal
cavity and tongue (10). Incorporation of the methyl group into
biomolecules would lengthen the half-life of clearance.
The appearance and clearance of MBN and [methyl-14C]MBN and [benzyl-7-'4C]MBN-derived radioactivity from the
blood were compared graphically (Chart 3). The percentage of
unmetabolized parent compound remaining in the blood was
calculated using the equation for whole-blood clearance of
MBN.5 The percentage of radioactivity present in the blood
was calculated from densitometer readings. Methyl and benzyl
moiety-derived dpm equivalents, representing both parent
compound and metabolites, were cleared more slowly than
MBN alone. In the first 5 to 10 mm after injection, methyl and
benzyl dpm equivalents increased at approximately the same
rate, reflecting the initial distribution of the intact parent mole
cule. Thereafter, benzyl dpm equivalents rose faster than
methyl dpm equivalents, probably due to entrance of the oxi
dized benzyl moiety-derived metabolites into the blood. As
shown by the radioautograph at 15 mm (Fig. 2a), benzyl
1924
l@
I-
0
—0.034t
—0.038t
—O.021t
—O.31t
body
0
4
LU
0.
z
Dosewas2.1 mg,1 mCi/kg bodyweighti.p.
=
=
=
=
0.
TIME IN HR
Chart 3. Clearance of unmetabolized MBN or dpm equivalents derived from
[methyl-'4C]MBN
and(benzyl-7-'4C]MBN
fromthewholebloodof maleSprague
Dawley rats. Doses were: MBN (0), 4.7 mg/kg body weight i.p.; [methyl
‘4CJMBN
(is), 3.3 mg, 1 mCi/kg body weight i.p.; and [benzyl-7-'4CJMBN (0).
2.1 mg, 1 mCi/kg bodyweighti.p.
metabolites had been rapidly removed by the kidney and
accumulated in the urinary tract. As a consequence, benzyl
dpm equivalents in the blood fell sharply after peaking at 60
mm. Methyl dpm equivalents also peaked at 60 mm but cleared
more slowly (t112= 18 hr) than did the benzyl dpm equivalents
(t112 2 hr).
Nitrosamines require metabolic activation to alkylating
agents in order to exert their biological effects (8, 11). MBN
can be oxidized to either a methylating or a benzylating species
(7, 18) which could react with cellular nucleophiles yielding
methylated or benzylated macromolecules or with water to
produce methanol or benzyl alcohol. The alcohols can be
oxidized further to the corresponding aldehydes and acids by
alcohol and aldehyde dehydrogenases (4, 12). The oxidized
metabolites would be generated within the cell and all are
either irritants or capable of inflicting tissue damage (16).
During ensuing regenerative processes, cell division may pro
vide an opportunity for incorporation of the carcinogenic lesion
into the genetic code. The oxidized metabolites of MBN may
be acting as cocarcinogens; noncarcinogens which enhance
the carcinogenicity of MBN, in this case by necessitating cell
repair and division which may increase the probability of lesion
fixation and eventual tumor development. Stimulation of liver
cell proliferation
via partial hepatectomy
has been used to
increase the yield of tumors following administration of DMN
(2, 3) and aromatic hydrocarbons, nitrosamines and nitrosam
ides, aromatic amines, and miscellaneous carcinogens (20).
Liver cell necrosis and the ensuing compensatory cell prolif
oration following administration of N-nitrosodiethylamine have
been shown to play an important role in the induction of
preneoplastic lesions (25). The carcinogenic effect of MBN
may be enhanced by the inability of the esophagus, nasal
cavity, and lung to readily clear the methylated or benzylated
macromolecules or oxidized metabolites which arise during
nitrosamine metabolism.
CANCERRESEARCHVOL. 40
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Tissue Distribution
ACKNOWLEDGMENTS
We wish to thank Dr. Robert Liss for use of the radioautography facilities at
Arthur D. Uttle. Inc., Cambridge, Mass. We also wish to thank Bruce McPherson,
Phil Schepis, and Dick Lauterno for instruction and advice.
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JUNE1980
1925
Downloaded from cancerres.aacrjournals.org on June 18, 2017. © 1980 American Association for Cancer Research.
P. L. Kraft and S. A. Tannenbaum
NASAL
CAVITY
ASAL
LUNG
AVITY
SPLEEN
KIDNEY
LIVER
,A •‘I
@
@.-
@
\
‘__•@t.
(@,_:
‘I,?
r't
1.
I.
TONGUE
NASAL
CAVITY
HEART
FORESTOMACH
LIVER
UPPER SMALL
INTESTINE
Ia
SPLEEN
URINARY
TRACT
2a
NASAL
CAVITY
KIDNEY
@
t\
@
!s__.@ .@‘.
@
TONGUE
SALIVARY
GLAND
LIVER
Ib
ESOPHAGEAL
ENTRY
INTO STOMACH
@
ESOPHAGUS
THYMUS
LIVER
IC
Fig. 1. Radioautographs of male Sprague-Dawley rats 15 mm (a), 7.25 hr (b),
and 24 hr Cc)after p. injections of [methyl-4C)MBN (3.3 mg, 1 mCi/kg body
weight).
1926
LIVER
NASAL
CAVITY
LARGE
INTESTINE
2b
LUNG
\
TONGUE
LIVER
LARGE
2c
INTESTINE
Fig. 2. Radioautographs of male Sprague-Dawley rats 15 mm (a), 7.25 hr (b).
and 24 hr (c) after i.p. injections of [benzyl-7-'4C]MBN (2.1 mg, 1 mCi/kg body
weight).
CANCERRESEARCHVOL. 40
Downloaded from cancerres.aacrjournals.org on June 18, 2017. © 1980 American Association for Cancer Research.
@
:@ @‘
Tissue Distribution
ESOPHAGEAL
LUNG
of[14C]MBN
ENTRY
INTO STOMACH
,,
LIVER
30
NASAL
CAVITY
---p
3b
NASAL
CAVITY
t@i@
.:@
LIVER
3c
Fig. 3. Radioautographs of male Sprague-Dawley rats 3 days after i.p. injec
tion of [methyl-'4C]MBN (3.3 mg, 1 mCi/kg body weight) (a, b) and (benzyl-7-
‘4C)MBN
(2.1 mg,1 mCi/kg bodyweight)(c).
JUNE1980
1927
Downloaded from cancerres.aacrjournals.org on June 18, 2017. © 1980 American Association for Cancer Research.
Distribution of N-Nitrosomethylbenzylamine Evaluated by
Whole-Body Radioautography and Densitometry
Patricia L. Kraft and Steven R. Tannenbaum
Cancer Res 1980;40:1921-1927.
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