FILE MEMORANDUM
September 25, 1974
DISCUSSION OF COLLABORATIVE BIOLOGICAL/BIOCHEMICAL
RESEARCH
A further meeting took place on September 23,
1974, between
Ms. J. Johnson, Dr. M.H. Bilimoria, Mr. R.S. Wade
and Dr. T.A. Smith
of ITPL, Drs. J.C. Hogg and S. Inoue of McGill and
Dr. H.P. Witschi
of UniversitA de Montrdal.
Four projects were discussed in the order given in
the
memorandum of September 197
1. Transformation of Carcinogens by AHH:
In the actual experiment, six animals per dose
level will
be needed for statistical significance. A standard
exposure of
5 cigarettes was accepted. The enzyme has to be
obtained from
whole lung homogenate or from its microsomal
fractions. MHB refered
to the possible use of a double beam
spectrophotometer to distinguish
between effects on.different cytochromes of the
P450 group, of
possible relevance to cancer.
It was confirmed that after training by HPW at U.
de M.,
the exposures and subsequent steps will be done at
McGill.
2. Development of.Protective Enzyme Systems
All four enzymes could possibly be measured on one
lung.
No one yet knows whether these enzymes will change
due to smoke, and
of course even if they do, the meaning of such
change would be
unclear. It was agreed that an exposure to smoke
of 5 cigarettes would
be sufficient, not 10-20 cigarettes as originally
suggested. It was
agreed that the best approach would be to take 1
lung (or lung lobe)
per animal for microscopy, and homogenise the
other in preparation
for the enzyme assays. The techniques for the
assays are simple to
carry out, making this a much shorter study than
Project 1. HPW
suggested that straight forward histology would be
the best approach
at first.
3. Biosynthetic Processes in Tracheal Mucosa
HPW believes this technique will be quite
difficult to develop.
He will oversee this development stage at U. de M.
Then the method
can be transfered for the exposures and
experiments to McGill. It may
be possible to get the tracheal mucosa samples
from the animals used in
Project 2.
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4. Signs of Lipid Peroxidation in Membranes of
Specific Cells
Again this will be a difficult technique to get
working, but
once successful, it could be*the most rewarding
project. A good, pure
cell population will be needed for this, and
methods for obtaining such
a population are available in the literature.
OVERALL PROGRAMME
JCH believes that this programme can be managed
wi'thout too
much difficulty. It involves at least one year's
work. It was
agreed that an application for a grant should be
worked out for
initially one year for the preliminary studies,
with the written under-
standing that, if successful, a further grant for
a longer period would
be required.
A proposal from RSW was accepted, that JCH should
submit the
application for a CTMC grant as coming from
McGill, with MH8 and JJ
participating through ITPL, and HPW acting as a
consultant. This will
be kept entirely divorced from JCH's present grant
which he hopes to
get renewed for 3 years (With this he hopes to
progress from animal
lung examinations to study of surgical samples of
human lungs). The
reimboursement of HPW would be done directly from
the CTMC.
Working under his MRC grant, HPW does not have to
worry about
getting materials for assays over the next 2
years. If the project is
successful and long-running, then the politics of
such a system would
be uncertain. Previously MRC would not allow
grantees to get money
from elsewhere, but regulations are now more
flexible.
JCH should have no problem in working out his
required budget.
He is presently employing a man half-time for
animal exposure, and the
proposed work could be handled by simply employing
the same man full-time.
A further budget would then be needed for
materials for microscopy.
JCH suggested that JJ, MHB and HPW visit McGill to
assess what equipment
would be needed there for the biochemical work.
This visit is arranged
for September 30, (similarly, we must consider
what equipment, if any,
is required here for the related biochemical
work).
In preparation for the grant application, HPW will
prepare
for JCH an expanded version (with references) of
his outline list of
project proposals as soon as possible. JCH will
then put this together
in an overall proposal. A copy of this will be
sent to R.M. Gibb
before JCH submits it formally through McGill to
CTMC.
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If the CTMC should turn down the application, JCH
indicated
that it now appears possible for work to be
carriedout in the Pathology
Dept. at McGill and supported by an individual
company with the
arrangements being made through the McGill
Contracts Office (as is
common in certain other faculties).
Priorities for Projects were discussed briefly.
JCH was more interested
in Project 1. and would tend to put that first.
However, in terms of
animal exposure and microscopy, there is no reason
why all 4 should not
be handled, so that the order of priority could be
dependent on the
biochemistry.
RSW reported that Dr. Binns had been contacted on
the importance
of deciding on a smoking machine for animal
exposure, and it was agreed
that it would be best if Southampton and Montrdal
were to use the same
type of machine. HPW mentioned that he had asked
Dietrich Hoffmann
about inhalation machines. The latter's advice had
been that the only
suitably versatile one worth considering was the
Dontenwill smoker.
On the question of publication of results, JCH
said that
McGill always insists on open publication oF
results. There would be
no problem in joint authorship with HPW of the U.
de M. or with MHB
and JJ of ITPL (JCH quoted an exam 1e of a model
of emphysema being
passed to McGill from Merck-Frosst~.
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BATCo document for Province of British Columbia 20
April 1999