USE OF TRANSPLANTABLE TUMORS AND CELL LINES IN ANIMALS

June 3, 1996

To: Investigators Using Transplantable Tumors and Cell Lines in Animals

From: Robert L. Harris, D.V.M.
Director of Laboratory Animal Services

Subject: Approval Procedure for Tumors and Cell Lines

Attached is a Standard Operating Procedure (SOP) for your use of transplantable tumors or cell lines in animals. Assuming that you have indicated a specific cell line that you will be using, the SOP is your approval to use that cell line in accordance with your animal use protocol as approved by the ACFC.

The SOP for transplantable tumors is similar to that for use of hazardous substances in animals. Laboratory Animal Services considers transplantable tumors as "biohazards" for several reasons. It is well documented that transplantable tumors and cell lines can be contaminated with animal or human pathogens which can be transmitted to the recipient animal. (See Nicklas, Ref. 2) These pathogens can be "biohazards" for either people and/or animals. Such pathogens can alter your research, cause clinical disease in your animals or those of other researchers, and/or cause disease in people. Thus it is important that we know (1) when you use such a tumor in the animal facility, (2) where the tumor comes from, and (3) what is known about the microbiological status of the tumor (i.e. viral or other contaminants). In addition, primary human tumors must be used under guidelines for human "blood-born pathogens", and may be subject to additional regulations.

Transplantable tumors are essentially "time-capsules" from whenever the tumor was frozen for storage. In many cases, these tumors originated at a time when many rodent colonies were enzootically infected with multiple infectious agents. One recent study showed that 25% of tumors examined were contaminated. (Note: ATCC does not test tumors for viral contaminants.) Animal tumors (e.g. mouse-derived tumors in mice) can be contaminated with animal pathogens of clinical concern for your animals. The only human pathogen frequently encountered in rodent tumors is lymphocytic choriomeningitis virus (LCM virus). (See Dykewics, Ref.1) Established human tumors, which are generally grown in hamster cheek pouches, or in athymic nude mice and rats, may be contaminated with LCM when passed in animals. In one lab, LCM persisted as a contaminant for 17 years of animal passages. (Ref. 2). Primary human tumors can be infected with agents such as AIDS and hepatitis. Use of these tumors, in animals or in in vitro culture, may be subject to blood-borne pathogen regulations.

Viruses which contaminate transplantable tumors may not cause clinically apparent disease in the transplant host or other animals it infects. Nevertheless, these viruses can have serious consequences for researchers trying to use infected animals.

Transplantable tumors are an important research tool. It is our hope that by following the general procedures that follow, and any specific procedures outlined in your SOP, you can conduct your research while not endangering animals and people in the animal facility. If you have questions or problems, please contact Dr. Robert Harris or Dr. Stephen Curtis in LAS at 732 445-4168.

GENERAL GUIDELINES FOR USE OF TRANSPLANTABLE TUMORS AND CELL LINES IN ANIMALS

Laboratory Animal Services

Rutgers, The State University of New Jersey

June 3, 1996

1. Approvals are for specific tumors from specific sources. Additional approval is required for new tumors.
2. Notify LAS each time you use a transplantable tumor. This can be done by providing this information on the animal order form sent to the LAS facility manager. (Tumor use may be only one of many procedures in an approved animal use protocol. LAS needs to know which animals on a protocol are receiving tumors.)
3. Record all tumor injections or transplants on the animals’ cage card. Include the date, and the name of the tumor. For hybridomas, include the name of the myeloma used as well as the designation of the hybridoma. Include the words "TRANSPLANTABLE TUMOR".
4. Tumor bearing animals must be monitored closely for adverse effects of tumor growth. For solid tumors, the general guideline is that tumor mass should not exceed 10% of body weight. For hybridomas, follow the ACFC’s "SOP for Monoclonal Antibody Production", unless other procedures are approved as part of your protocol.
5. Report any illness in your animals to LAS, and include the information that the animal had received a transplantable tumor.
6. It is not necessary to label animals, cages, or animals with a "BIOHAZARD" sign.

References:

1. Dykewics et al., Lymphocytic choriomeningitis outbreak associated with nude mice in a research institute. JAMA 267(10): 1349-1353, 1992.
2. Nicklas et al., Contamination of transplantable tumors, cell lines, and monoclonal antibodies with rodent viruses. Lab An Sci. 43(4):296-300, 1993.