Radiation-induced morphologic changes in the rhesus monkey (Macaca mulatta) brain.

The right cerebral hemisphere of 24 rhesus monkeys scheduled for necropsy at the completion of another project were studied histopathologically 1-30 days after a single dose of 60Co-irradiation. Histopathologically, inflammation and gliosis consistently occurred at specific time points but varied in severity between individuals. Multifocal hemorrhage, edema, and an acute neutrophilic inflammatory response were observed initially whereas perivascular accumulations of lymphocytes were observed in specimens at the end of the study. Microglia/macrophages were most prominent during the first week after irradiation, whereas astrocytes were reactive throughout the observation period. The early clinical manifestations of the central nervous system (CNS), because of brain irradiation in humans, correspond temporally with acute vascular responses, acute and subacute inflammatory cell responses, and subacute demyelination and reactive astrocytic and microglial responses observed in the rhesus monkey. Initial responses of the CNS to gamma-irradiation may have potential implications for the development of radiation-induced late injury of the CNS.

Comparison of kidney weight and volume to selected anatomical parameters in the adult female rhesus monkey (Macaca mulatta).

In this study, the normal distribution of renal weight and volume was determined and the correlation between the weight and volume and various skeletal measurements taken from radiographs and at necropsy was assessed. Values from 136 female monkeys with complete data (including all bone, radiographic, and kidney measurements) were analyzed. The mean kidney weight was 13 g with a standard deviation (SD) of 2 g. The mean kidney volume was 12 ml, SD 2 ml. The estimation of kidney weight and volume from bone length, age, or body weight was not reliable according to statistical analysis of our data. We did find that all apparently normal adult female rhesus monkeys typically have similar sized kidneys. This information is useful in that it reduces concerns about consistency in experimental subjects.

Reliable establishment of human sarcoma xenografts in the nude rat.

Purpose. The ability to establish consistent human tumor xenografts in experimental animals is a crucial part of preclinical investigations.The goal of this study was to develop a method of establishing a human tumor xenograft in the leg of a nude rat for evaluation of new surgical and molecular methods of treatments of human extremity sarcoma.Methods and results. Initial attempts to produce sarcoma nodules by subcutaneous injection of a human leiomyosarcoma tumor cell suspension (SKLMS-1) resulted in tumor nodule formation in only four of 10 sites (40%).The xenograft method was modified to include younger nude rats of a different source and substrain (HSD:rnu/rnu, 5-9 weeks old), treated with 500 cGy whole-body irradiation, and the transplantation of tumor cells or small tumor fragments which had been embedded in Matrigel.These changes improved the tumor take rate per site to 52/52 (100%).Tumor nodules demonstrated rapid and progressive growth and histological features consistent with the original human sarcoma.Discussion. Successful human leiomyosarcoma establishment in these nude rats permits the investigation of sarcoma biology and treatment with surgical procedures for which a mouse model would be inadequate. In this study we identified modifications in technique which enhanced the xenografting of a leiomyosarcoma cell line in nude rats; these techniques may increase tumor take rates for other tumor types as well.

Postirradiation sarcomas in Sprague-Dawley rats.

A series of radiation-induced neoplasms occurred in Sprague-Dawley rats 4-8 months after irradiation of a single hind leg with 60Co gamma rays. The rats were exposed to fractionated cumulative doses that ranged from 0 to 106 Gy. Osteosarcomas, malignant fibrous histiocytomas and fibrosarcomas developed in the radiation fields of a number of the rats in the higher-dose groups. Tumors did not develop throughout an 8-month observation period in rats that received doses of only 0 or 46 Gy. The most common postirradiation sarcomas in humans are osteosarcoma, malignant fibrous histiocytoma and fibrosarcoma. The Sprague-Dawley rat may serve as a good animal model in studying the development of sarcoma in humans after regional radiotherapy.

Stenosing colonic adenocarcinoma in a female rhesus monkey.

Laparoscopic surgery was performed on a 16 year-old female rhesus monkey presenting with chronic lethargy and inappetence. The procedure revealed a "napkin-ring" stricture located in the ascending large colon. Histologic evaluation of the colonic lesion exhibited large numbers of irregular acini lined by a single layer of well-differentiated neoplastic epithelial cells. Based on the gross and histopathologic findings a diagnosis of adenocarcinoma of the proximal colon was made.

Glioblastoma multiforme arising in the irradiated spinal cord of a rhesus monkey (Macaca mulatta).

An adult female rhesus monkey that had received 44.0 Gy of cobalt 60 radiation to 8 cm of the cervical and upper thoracic spinal cord approximately 2.8 years postirradiation developed a sudden onset of self-mutilation and loss of function of the right arm followed progressively by loss of function of the left arm and terminally bilateral paresis of the legs. Histopathologic examination of the cervical spinal cord revealed a glioblastoma multiforme that extended from the cervical medullary junction to the sixth cervical vertebrae. Because of the infrequent occurrence of spontaneous neoplasia in rhesus monkeys and the location in the radiation field, the glioblastoma is believed to be radiation induced.