The rationale behind the suggestion that Brca1 might be overexpressed when animals have both ovarian and mammary tumors implanted is confusing, as the normal BRCA1 protein usually repairs double-stranded breaks in DNA and thus prevents the formation of these tumors. Consistent with the function of BRCA1 as a tumor suppressor, only women who carry a mutation in the gene BRCA1 have a much higher risk of developing breast and ovarian cancer. The suggestion that implantation of ovarian or mammary tumors may result in overexpression of Brca1 raises some scientific questions, which may not be relevant to the IACUC, as it is charged with focusing its review on animal welfare. Our comments will thus also focus on animal welfare.
We feel that the progression of events described in this scenario resulted from a misunderstanding on the part of the investigator, likely stemming from a lack of communication regarding what should be included in an animal care and use protocol. The information provided in the protocol about drugs and treatments used was clearly inadequate and should be corrected immediately. The IACUC should request an addendum or a revised protocol from the investigator specifying that mice experiencing tumor-related illness will be treated with cisplatin, a chemotherapeutic agent commonly used for the treatment of ovarian cancer. In the addendum, Birnbaum should describe specific conditions under which chemotherapy would be used, as well as the dose and frequency of administration. Issues related to potential risk of handling cages and bedding of drug-treated mice and specific methods for disposal should also be included. Work on this protocol should be discontinued until the addendum can be reviewed and approved, and its review should be expedited so that the work is only minimally disrupted. This situation should be reported to the Institutional Official and documented in the record, but it may not be necessary to officially report it to OLAW or the granting agency. We believe that Great Eastern should contact OLAW by telephone to assure that all appropriate measures are being taken and should follow any advice offered by OLAW.
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