Time of death of CNS tumor-bearing rats can be reliably predicted by body weight-loss patterns

Abstract

A request by the Institutional Animal Care and Use Committee for an alternative to death as an end point in a cancer research project using a rat brain 9L tumor cell model led to a search for reliable criteria for predicting time of death in this type of experiment. These experiments evaluated the therapeutic effectiveness of radiation alone, continuous intracerebral infusions of 5-iodo-2-deoxyuridine (IUDR) alone, and a combination of both therapies. We found that a characteristic pattern of body weight changes occurs after injection of 9L tumor cells into the brain ventricles or parenchyma. The initial phase was characterized by a loss of body weight which appeared to be related to surgery and, in the irradiated groups, to the subsequent doses of radiation under anesthesia on days 4, 6, and 7. After this initial phase (phase 1), a second period of weight change (phase 2) which was characterized by an overall gain of body weight interrupted temporarily in 76 out of the 149 rats by reversible episodes of weight loss of 1 to 5 days duration. The length of this phase 2 weight gain period was significantly extended by XRT-IUDR treatment in the rats with intraparenchymal tumors. The third and final phase consisted of a period of irreversible weight loss which may be related to cachexia. The third phase was similar in duration for control, XRT, IUDR and XRT-IUDR groups of rats and had a mean length of 9.8 +/- 0.27 days.(ABSTRACT TRUNCATED AT 250 WORDS)