Philip Morris
Comments on Abstract by K. C. Snell and H. L. Stewart Entitled, 'induction of Pulmonary Adenomatosis in Dba/2 Mice by the Oral Administration of Dibenz(A,H)Anthracene,'
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Document Images
of Pulmpnary Adenomatosis in D~BAf2 Mice by the Oral Administration of
'Comnents on Abstract by K. C. Snell and H. L. Stewart entitled., "Induction
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Dibenz(a,h)anthraeene," published in Authors' Abstracts, Eighth Inter-
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national Cancer Congress,.Mascow, U.S.S.R., July 22-28, 1962:
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s T t`Y` ~~: The attached abstract shows that for a relatively sma]l group of
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5
27
mice who were fed an aqueous olive oil emulsion of
enz
bi~
anthracene,
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an unstated number of animsls developed alveologenic carcinoma of the
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lung which Dr. Steward .~.. also called pulmonary a
denoma . ~ ^
tosis. In contrast
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to the abstract by Fylev, this lesion is not one which would be con- `'~~~y
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sidered to be strictly comparable with the human carcinomaof the lung Mf7~s~;~ ~
f
said to be associated with smoking.
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Attachment: copy of abstract
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I NDUCTION OF LUNG CANCER IN RATS BY
INTRATRACHENAL INSUFLATION OF CANCEROGENIC
HYDROCARBONS ._. ...
L. N. PYLEV
USSR, MOSCOW
; 9,10-dimethyl-1,2-benzanthracene (DMBA) was inted to rats intratracheally
a:- by intubation; Wistar and noninbred rats were used. In some groups one intubation
i; pf 2.5 mg DMBA was performed, in other groups DMBA was introduced three or
"five times (2mg per intubation; the total dose amounting respectively to 6 and 10 mg),
"'~ In other experiments 3,4-benzpyrene was introduced in.the doses 5 mg five and seven
z~ n. times (that is, in the total doses 25 and 35 mg). The interval between injections was '
;"about a'month. Cancerogen was added to the colloid protein solution containing small
amounts of Indian ink.
Lung cancer appeared approximately in one-third of the animals which have
survived more than 5 months from the beginning of the experiment. Most of the lung
tumours were histologically squamous carcinomas; but there were several cases of
adenocarcinoma. Both types of neoplasms gave methastases in peribronchial, para-
thracheal and paraverthebral lymph nodes.
Tumour development was preceded by changes, which one may characterize as L ~
precancerous: focal metaplasia of bronchial epitheliums, papillomas and polyps of
bronchial epitheliums, adenomas and papillomas. -
Thus, the possibility of the systematic induction of experimental lung cancer in
rats was shown.
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K. C.- S NE L L and H. L. S T E W A R T USA, BETHESDA
,
1 NDUCTION OF PULMONARY ADENOMATOSIS IN DBA/2
MICE BY THE ORAL ADMINISTRATION OF DIBENZ(A,H)-
------_ . ..-._.~ .
All of 14 male and 13 female DBA/2 mice that were given, in place of drinking
water, an aqueous olive oil emulsion of dibenz (a,h) anthracene for 200 days or longer,
developed pulmonary adenomatosis. The lesion was found also in one control! mouse
given the olive oil emulsion without dibenz (a,h) anthracene. Mice that drank the
emulsion containing dibenz (a,h) anthracene developed alveologenic carcinoma, tumours
of the mammary gland, precancerous lesions of the small intestine and haemangio-
endotheliomas involving the pancreas, mesentery, and abdominal lymphnodes. These
and other lesions induced by the treatment, as well as spontaneous lesions to which
DBA/2 mice are subjects, will be described and discussed.
INFLUENCE OF SOME NUTRITIONAL FACTORS ON URE-
THANE-INDUCED PULMONARY ADENOMAS IN MICE
F. A. FRENCH, . .,
A. H O S K I N G and J. F R E N C H USA. SAN FRANCISCO
Previously we have reported that high but well tolerated doses of nicotinamide,
given orally, significantly reduce the number of pulmonary adenomas in urethane
treated strain A mice. These effects were observed with mice at different age levels,
from different sources, on diverse basic diets and with a variety of dosage schedules.
Deprivation of exogenous niacin erratically increases the incidence of pulmonary
adenomas. Subsequently It has been found- that high levels of nicotinic acid have no
effect on the tumour incidence. In experiments where nicotinamide was given before
overlapping and after urethane treatment the only significant result was that the
antitumour effect is roughly proportional to the length of treatment after the initiation
of carcinogenesis. Choline does not negate the antitumour effect of nicotinamide and
hence the observed effects are not due to methyl group deprivation.
Also we have found, in independent experiments, that choline in the form of its
citrate and tartrate salts significantly decreases the number of tumours. Choline bitar-
trate gave 7.60 ± 0.57 and controls 10.05 ± 0.59 tumours per mouse (groups of 40
mice), p - 0.0039. Choline dihydrogen citrate gave 3.60 t 0.32 and controls 5.86 t
t 0.42, p 0.0001. Preliminary experiments indicate that Inositol is also an active
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