IACUC Policy: Tumor Production
Policy # IBT-203.00 IACUC Approval: February 27, 2014

Purpose:
The purpose is to minimize the pain and distress that rodents may experience when used in experimental protocols involving the production of in vivo neoplasia.

Scope:
This policy applies to all IACUC approved protocols subject to oversight by Texas A&M Health Science Center.

Responsibilities:
Appropriately trained research staff are expected to monitor rodents with tumors in accordance with this policy. Animal care staff will conduct routine health surveillance and any concerns will be reported to the veterinary staff.

All efforts will be made to contact research staff should an animal require euthanasia per the veterinary staff so that tissues can be collected. If research staff cannot be reached, rodents meeting criteria for humane endpoints will be euthanized at the discretion of the Attending Veterinarian.

Definitions:
In vivo neoplasia – the process of abnormal and uncontrolled growth of cells in a living animal. The product of neoplasia is a neoplasm (a tumor).
Moribund-Clinically irreversible condition leading inevitably to death.
Cachectic-General weakness with extreme loss of weight.
Metastasis-Spread of cancer.

Procedure: 

I. Site of tumor implantation

Choose a site that will have minimal impact on adjacent normal structures. The muscle distention caused by intramuscular implantation is considered painful, as are tumors which involve the eye. Ideally, tumors should be placed so that their growth will not interfere with normal mobility and functions such as eating, drinking, defecation and urination. Most preferred is subcutaneous or intradermal implantation in the flank.

II. Tumor burden-Criteria for euthanizing animals with tumors

Optimally, studies are terminated when animals begin to exhibit clinical signs of disease if this endpoint is compatible with meeting the research objectives. Such endpoints are always preferable to death or moribundity as endpoints since they maximize animal welfare and minimize pain and distress. Efforts should be made to minimize pain and distress experienced by animals used in research. Exceptions to these criteria must be reviewed by the IACUC on a case by case basis.

  1. Total tumor burden (sum of all tumors) is greater than or equal to 10% of the animal’s normal body weight (1 cm3 = 1g)
  2. Total tumor burden (sum of all tumors) exceeds 1.5 cm (mouse); 2cm (rat); in size in any direction.
  3. Significantly impedes ambulation
  4. Ulcerated or abscessed
  5. Causes significant pain or distress.
  6. Any animal found moribund, cachectic, or unable to obtain food or water
  7. Exhibit >20% weight loss

III. Monitoring 

  1. Health and clinical signs monitoring-A schedule of regular health monitoring that includes checking for clinical signs including weights should be detailed in the protocol and documented.
  2. Frequency of monitoring needs will vary by expected growth for the type tumor, aggressiveness of the tumor and metastasis potential.

Per OLAW: Animals should be observed frequently enough to detect signs of impending death so they can be euthanized in a timely manner. When increased morbidity or mortality is expected, a minimum of twice daily observation is recommended. Animals not likely to survive until the next scheduled observation should be euthanized. In situations where animals are often found dead, closer and more frequent observation for moribund animals should be considered to reduce spontaneous deaths.

References:

  1. Animal and Plant Health Inspection Service, USDA. US Animal Welfare Act (AWA 1990) and Regulations (PL-89-544, as amended, 7USC Ch. 54) 2008. CFR Title 9, Subchapter A - Animal Welfare. U.S. Government Printing Office, Washington, D.C.
  2. National Research Council. Institute for Laboratory Animal Research. 2011. Guide for the Care and Use of Laboratory Animals. Public Health Service, Bethesda, MD.
  3. Public Health Service Policy on Humane Care and Use of Laboratory Animals http://grants.nih.gov/grants/olaw/references/phspol.htm.
  4. Silverman, Jerald, et.al. 2000. The IACUC Handbook: The Basic Unit of an Effective Animal Care and Use Program. Baltimore, MD.
  5. ARENA/OLAW Institutional Animal Care and Use Committee Guidebook, 2nd Ed. 2002.
  6. Bullard DE, Schold SC Jr, Bigner SH, Bigner DD (1981), Growth and chemotherapeutic response in athymic mice of tumors arising from human glioma-derived cell lines. J Neuropath Exp Neurol 40:410-427.
  7. Hamm (1995), Proposed institutional animal care and use committee guidelines for death as an endpoint in rodent studies. Contemp Top Lab Anim Sc 34:69-71.
  8. Sung C, Dedrick RL, Hall WA, Johnson PA, Youle RJ (1993), The spatial distribution of immunotoxins in solid tumors: assessment by quantitative autoradiography. Cancer Research 53: 2092-2099.
  9. Tomayko MM and Reynolds CP (1989), Determination of subcutaneous tumor size in athymic (nude) mice. Cancer Chemother Pharmacol 24:148-154.
  10. Welch DR, Chen P, Miele ME, McGary CT, Bower JM, Stanbridge EJ, Weissman BE (1994), Microcell-mediated transfer of chromosome 6 into metastatic human C8161 melanoma cells suppresses metastasis but does not inhibit tumorigenicity. Oncogene 9: 255-262.
  11. http://www.ucuca.umich.edu/guideproc.htm
  12. Morton and Griffiths (1985), Veterinary Record 116:431-431
  13. Montgomery (1990), Cancer Bulletin 42:230-237
  14. Montgomery, C.A. Jr. (1990), Cancer Bulletin 42:230-237 and appeared in AWIC Newsletter, Spring 1995 6:4
  15. Hickman DL, Swan M. (2010) Use of a Body Condition Score Technique to Assess Health Status in a Rat Model of Polycystic Kidney Disease. JAALAS. 49(2): 155-159.

History:
Version 00 – Initial Approval: February 27, 2014