Rodent Tumor Production

Purpose

UConn Health’s Institutional Animal Care and Use Committee (IACUC) and the Attending Veterinarian are responsible for ensuring that all research animals are provided adequate veterinary care. This policy details requirements regarding tumor production to include implantable/inducible tumors, evaluating tumor growth, ascites produced by tumors, and endpoints and exemptions.

Action

Implantable/Inducible Tumors

  1. Tumor implantation sites should be chosen to minimize damage to adjacent normal structures. The IACUC recommends implanting tumors on the dorsum or flank of an animal, as these areas will likely have minimal or no site-related morbidity.
  2. Sites involving the face, limbs, or perineum should be avoided as there is little to no space for tumor growth and expansion.
  3. Intramuscular implantation should be avoided as this is considered to be painful due to the distention of the muscle by the tumor.
  4. Tumor implantation on the ventral surface of the body should also be avoided due to the risk of irritation to the tumor site in contact with the bedding and floor of the cage.

Evaluating Tumor Growth

  1. Animals that are on a tumor production study must be monitored by the PI staff at least once a week during the time when the tumor is not yet detectable, to observe when tumor growth has begun.
  2. After a visual or palpable tumor is evident, the animals must be monitored by the PI staff at least twice weekly. More frequent observations may be necessary based on tumor growth rate, study parameters, and general condition of the animals and will be detailed in the approved animal protocol.
  3. The general physical condition of the animals is the most important factor in effectively following the progression of tumors in rodents.
  4. When on the dorsum or flank of an adult rodent, tumors may be allowed to grow to mean diameters of 2.0cm in mice and 4.0cm in rats as long as the rodent remains otherwise healthy.
  5. Evaluating tumors in central areas of the rodents (e.g., bone, lung) can be challenging. Tumor size will likely not be useful and, because of the sensitivity of areas, a small tumor may cause severe clinical signs. For tumor models studying central body tumors, clinical evaluation of the animals take priority over the measured size of the tumor. The expected clinical signs and the humane endpoints of those signs must be clearly described in the protocol. The evaluation of clinical signs in an animal with a tumor burden of this type should include consultation with the attending veterinarian.
  6. Multiple tumors present other challenges. The concern of size for individual tumors is related to central necrosis, ulceration of skin overlying tumors, and abrasions. Multiple tumors that are individually smaller than the single tumor limit may not have the same negative sequelae as a single tumor. Multiple tumors may be allowed to grow up to 150% of the volume compared with the volume of a single tumor. Please note that the limitation on a single tumor will still be valid.
  7. Tumor ulceration may not necessarily require euthanasia, but it does potentially require more frequent monitoring and treatment of the ulcerated tumor. The care for ulcerated tumors is based on both the size of the ulceration and the clinical judgment of the veterinarian.
    • Pinpoint (<=2mm) ulcerations at the site of tumor injection must be monitored at least 3 times per week for worsening of the ulceration site.
    • Ulcerations up to approximately 25% of the surface area of the tumor must be monitored at least 3 times per week and must be reported to the CCM veterinary staff for evaluation and potential treatment. If animals with ulcerated tumors of this size are not under veterinary care, these animals must be euthanized.
    • Ulcerations of greater than 25% of the surface of the tumor must be euthanized.
Species Single tumor (max volume) Multiple tumors (max volume)
Mouse 4.2cm3 6.3cm3
Rat 33.5cm3 50.25cm3

Ascites Produced by Tumors

  1. In cases where tumors are expected to grow with an accumulation of ascites, rodents must be weighed prior to inoculation and subsequently be followed by weight measurements at regular intervals and this must be described in the approved protocol and based on the expected rate of fluid accumulation.
  2. When the body weight exceeds 120% of the initial weight, the rodents must be euthanized or the animal tapped. Ascites pressure should be relieved before abdominal distention is great enough to cause discomfort or interfere with normal activity.
  3. The abdominal tap should be performed by trained personnel using proper aseptic technique, with manual restraint or anesthesia, and by using the smallest needle possible that allows for good flow. This procedure must be described in the approved protocol.

Endpoints and Exemptions

  1. Endpoints must be determined and specified in the experimental protocol.
  2. If there is a strong scientific justification for maintaining tumors exceeding any of the guidelines described above, this must be detailed in the animal protocol and approved by the IACUC.
  3. For studies that involve some degree of morbidity – Pain/Distress category D or E should be checked and the applicable sections filled out in the Animal Care and use Protocol.

References

1. The Guide for the Care and Use of Laboratory Animals, 8th Edition, 2012. National Research Council

2. IACUC Guideline on Rodent Tumor Production, University of Pennsylvania.

3. Ulman-Cullere MH and CJ Foltz. 1999. Body Condition Scoring: A Rapid and Accurate Method for Assessing Health Status in Mice. Lab Anim Sci 49(3): 319-323.

Effective Dates: January 25, 2018 through December 31, 2020