Examination of the ovotoxicity of 5-fluorouracil in mice.

PURPOSE: Undesirable side effects of cancer treatments are common and include damage to the ovary, and depletion of the follicle reserve, which if severe enough, can lead to infertility and early menopause. Antimetabolite drugs, such as 5-fluorouracil (5-FU), are not considered to be detrimental to the ovary, but the ovotoxicity of 5-FU has not been evaluated in any detail. The purpose of this study was to evaluate the effects of 5-FU on follicle number. METHODS: In this study, adult female C57Bl6 mice (n = 4-6 animals/group) received a single dose of saline or 5-FU (150 mg/kg) and markers of ovarian damage and follicle depletion were assessed 12 h and 7 days later. RESULTS: Exposure to 5-FU did not alter primordial and primary follicle numbers. Atresia of secondary and antral follicles was increased significantly 12 h after 5-FU treatment, but atresia rates returned to levels similar to that of saline treated controls at 7 days. The number of corpora lutea were reduced 7 days after exposure to 5-FU, possibly as a consequence of earlier follicular atresia. CONCLUSIONS: These findings suggest that a single dose of 5-FU is mildly ovotoxic, but any effects on ovarian function are likely transient because the primordial follicle population is not depleted. Collectively, these data support the notion that 5-FU is unlikely to impact on the long-term fertility of women.

Post-natal imprinting: evidence from marsupials.

Genomic imprinting has been identified in therian (eutherian and marsupial) mammals but not in prototherian (monotreme) mammals. Imprinting has an important role in optimising pre-natal nutrition and growth, and most imprinted genes are expressed and imprinted in the placenta and developing fetus. In marsupials, however, the placental attachment is short-lived, and most growth and development occurs post-natally, supported by a changing milk composition tailor-made for each stage of development. Therefore there is a much greater demand on marsupial females during post-natal lactation than during pre-natal placentation, so there may be greater selection for genomic imprinting in the mammary gland than in the short-lived placenta. Recent studies in the tammar wallaby confirm the presence of genomic imprinting in nutrient-regulatory genes in the adult mammary gland. This suggests that imprinting may influence infant post-natal growth via the mammary gland as it does pre-natally via the placenta. Similarly, an increasing number of imprinted genes have been implicated in regulating feeding and nurturing behaviour in both the adult and the developing neonate/offspring in mice. Together these studies provide evidence that genomic imprinting is critical for regulating growth and subsequently the survival of offspring not only pre-natally but also post-natally.

Hyperthermia for treatment of ocular squamous cell tumors in cattle.

Fifty-six benign ocular squamous cell tumors and 20 squamous cell carcinomas were subjected to hyperthermia (50 C for 30 sec/cm2 of tumor surface) created by radio-frequency current from an electrothermal device. Of the 76 tumors, 60 (49 benign and 11 malignant) regressed completely following a single treatment. Among the remaining 16 tumors, 7 benign tumors and 2 squamous cell carcinomas regressed completely following a second treatment, whereas 5 carcinomas regressed partially and 2 carcinomas failed to respond after the second treatment, whereas 5 carcinomas regressed partially and 2 carcinomas failed to respond after the second treatment. Thus, 90.8% of the tumors regressed completely, and all of these sites were free of visible lesions 5 1/2 months after the initial treatment. Of 69 sites that were tumor-free at 5 1/2 months, 42 were available for observation at 1 year; all 42 sites were free of tumor. Squamous cell tumors developed subsequently at other ocular or adnexa

Myonecrosis induced by rattlesnake venom. An electron microscopic study.

The myonecrotic effect of rattlesnake (Crotalus viridis viridis) venom on mouse skeletal muscle was studied. The biceps femoris muscle was examined with the electron microscope after one-fourth the LD(50) of the crude venom was injected into the gracilis and semimembranosus muscles. Focal areas of myonecrosis were abundant. Injured fibers contained dilated sarcoplasmic reticulum, disoriented, coagulated myofilamentous components and condensed, rounded and enlarged mitochondria. The external lamina and sarcolemma remained intact in many fibers. Hemorrhage was apparent in the endomysial connective tissue, and hemolysis was discernible. In areas where the erythrocytes were tightly packed between the muscle fibers, there was disruption of the external lamina and sarcolemma. Degeneration of the fibers in these areas was pronounced. These findings correlate well with the breakdown of muscle fibers by various methods described in the literature. Myonecrosis induced by snake venom may serve as a useful model for studying muscle necrosis because of its rapid onset and relative ease of induction.