Growth and Development in Rats Given Recombinant Human Epidermal Growth Factor1-48 as Neonates
| Autor: | J. A. Anderson, Judith W. Henck, J. F. Reindel |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
medicine.medical_specialty
Recombinant Epidermal Growth Factor Injections Subcutaneous Preputial gland Motor Activity Biology Weight Gain Toxicology Subcutaneous injection Pregnancy Epidermal growth factor Internal medicine Toxicity Tests medicine Animals Genitalia Sexual Maturation Rats Wistar Habituation Skin Behavior Animal Dose-Response Relationship Drug Epidermal Growth Factor Neural Inhibition Organ Size Peptide Fragments Recombinant Proteins Rats Dose–response relationship Endocrinology Acoustic Stimulation Animals Newborn Toxicity Reflex Female Mitogens |
| Zdroj: | Toxicological Sciences. 62:80-91 |
| ISSN: | 1096-0929 1096-6080 |
| DOI: | 10.1093/toxsci/62.1.80 |
| Popis: | To assess effects of supraphysiologic doses of human recombinant epidermal growth factor(1-48) (rhEGF(1-48)) on neonatal rats, 10 litters of Wistar rats/treatment group were given 0 (formulated vehicle), 10, 100, or 1000 microg/kg daily by subcutaneous injection on postnatal days (PND) 1 through 6. Clinical signs, body weight, acquisition of developmental landmarks and reflexes, and behavior were monitored during treatment and for 5 weeks thereafter (to PND 42). A subset of animals was euthanized weekly from PND 7-28 and necropsied. Selected tissues were examined microscopically. Body weight gain at 1000 microg/kg during treatment was significantly less than control. Precocious incisor eruption, eye opening, vaginal opening, and preputial separation occurred at 100 and/or 1000 microg/kg. Acquisition of reflexes (negative geotaxis, wire maneuver, acoustic startle reflex, and visual placing) was delayed at 1000 microg/kg. Acquisition of adult locomotion was also delayed at 1000 microg/kg. These effects were transient, as locomotor activity at PND 28 and 42 did not differ from control. Effects on acoustic-startle responding persisted in females to final assessment on PND 42. Habituation to repeated acoustic stimuli was impaired, as well as response inhibition following a prepulse acoustic stimulus. rhEGF(1-48) induced structural changes in the skin, retina, kidney, oral and nasal mucosa, lung, and liver. Many of these changes were consistent with the expected mitogenic activity of rhEGF(1-48) and were transient in nature, as severity and incidence diminished with time. An exception was changes observed in the retina at 1000 microg/kg (rosettes/folds and focal defects in the outer nuclear/photoreceptor layers) that were still present 3 weeks after termination of treatment. Acceleration of developmental landmarks; suppression of reflexes, behavior, and somatic growth; and mitogenic responses in epidermal tissues have been reported in rodents treated with epidermal growth factor (EGF) derived from various mammalian species. These results demonstrate that a 48-amino acid fragment of human EGF produced by recombinant technology also induces such effects. |
| Databáze: | OpenAIRE |
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