Tumor Inoculation in Rodents. The purpose of
this document is to provide general end points for experimentally
induced neoplasia (tumors) in rodents. Investigators producing tumors
in rodents should use this document as a reference in preparing their
Protocols for Animal Care and Use. These general guidelines may not
be applicable in all cases. Alternate procedures should be clearly
described and justified in the Protocol for Animal Use and Care.
Background. Many tumors grow rapidly
and can compromise the health and well-being of the
research animals. If the tumor is subcutaneous or on
the skin's surface, it can become large enough to interfere
with the animal's locomotion, grooming, and ability
to access food and water. In addition, these tumors
can ulcerate and result in secondary bacterial infections.
If the tumor is growing in the animal's abdominal or
chest cavity, it can compromise respiration, food intake,
and in some cases, locomotion.
Policy. Each project involving tumor
production in rodents should define a set of conditions
under which the affected animals will be euthanized.
Use of survival time as an end point is rarely justifiable
and should be avoided. Animals should be euthanized
before their tumor burden becomes excessive and before
the animals become debilitated. Four general criteria
for euthanasia are given:
• Maximal tumor size should be limited to 10%
of body weight. Mice which have subcutaneous or skin
tumors should be humanely euthanized when the tumor
reaches 1.5 centimeters in diameter. Rats should
be euthanized if the tumor size exceeds four centimeters
in diameter. All animals should also be euthanized
if a tumor ulcerates prior to reaching this size.
• In some studies, either the tumor itself
or anti-tumor therapies may cause the animal to lose
condition. In these studies, adult animals should
normally be euthanized if adult animals lose 20%
of their original body weight, or if growing animals
attain a weight less than 80% of untreated controls.
• Some tumors, depending on type and location,
may interfere with the function of vital organs,
such as the lungs or digestive tract. If animals
are seen to be in distress (e.g. labored breathing)
due to an experimentally induced tumor, they should
be euthanized regardless of the size of the tumor
or the weight of the animal.
In addition, some tumors may interfere with locomotion,
making it difficult for the animal to reach food or
water. If the animal is unable to eat or drink, it
should be euthanized.
Animals in which tumors have been induced should be
checked at least three times weekly - either by the
principal investigator or his/her designee. Animals
that fall into any of the three categories listed above
should be reported to the principal investigator. The
principal investigator will examine the animal and
take appropriate steps within 24 hours of receiving
such a report.
In the case of very rapidly growing tumors or other
situations in which the progression of clinical signs
is likely to be rapid, the principal investigator or
his/her staff should examine the animals daily.
See also the NIH Guidelines to Humane Experimental
Endpoints
Scientific Merit Review of Protocol. A reviewer of
scientific merit should evaluate the science of the
project, not the procedures performed on animals or
the protocol. The project should be evaluated for quality
of the science and the impact it may have on its field.
Your review should address the following issues with
regard to the project:
1. Does this study address an important problem
or scientific question? Does the project employ novel
concepts, approaches or methods in addressing the
question?
2. Are the conceptual framework, design, methods,
and analyses adequately developed, well-integrated,
and appropriate to the aims of the project? Are the
aims of the project clear and reasonable in the context
of the project?
3. What new information is likely to result from
this study?
4. Is the investigator appropriately trained and
well suited to carry out this work?
5. What is the basis for your knowledge of the study:
grant proposal, published material, discussions,
etc.?
6. Do you have a conflict of interest which would
prevent you from making an unbiased evaluation?
7. Please include the name of the principal investigator
in your review. This will insure that the IACUC Office
can match scientific review letters with the correct
animal protocols.
Forms for scientific merit review in Microsoft Word
format are available for download
Please submit the completed scientific merit review
form to the IACUC Office, School of Medicine, WG-77,
10900 Euclid Avenue, Cleveland, Ohio 44106-4919. If
you have any questions please call the IACUC office
at 368-3815. Thank you.
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