Radiation Effects on Growth Are Altered in Rats by Prednisolone and Methotrexate

Schunior, Ann; Mullenix, Phyllis J.; Zengel, Anna E; Landy, Hal; Howes, Anthony E.; Tarbell, Nancy J.

doi:10.1203/00006450-199404000-00007

Cited by 29 publications

(9 citation statements)

References 21 publications

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“…This is probably associated with the poorer growth of body dimensions observed in the same animal group and with the possible testicular toxicity of the treatment. The present observation that female rats do catch-up better than males is supported by the earlier results of SCHUNIOR et al (34), where the body weight of the rats following a single injection of MTX at the age of 18 d returned to control levels by day 80, females recovering sooner than males.…”

Section: Discussionsupporting

confidence: 90%

Catch‐up growth and craniofacial dimensions following administrationof the antineoplastic agent vincristine to young rats

Karsila

Jahnukainen

Salmi

et al. 2000

European J Oral Sciences

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Decreased linear growth is a common problem during childhood anticancer therapy. Although catch-up growth may occur, short stature is sometimes permanent. A macroscopic experimental study was performed to investigate the catch-up growth of body and craniofacial structures of growing rats subjected to the antineoplastic agent vincristine. A total of 150 Long-Evans/Turku strain rats were randomly divided into one of two treatment or control groups. A group of 10-d-old rats was given a single s.c. injection of 0.0375 mg/kg vincristine, while another treatment group of 30-d-old rats received three injections of 0.05 mg/kg vincristine. All rats were killed at the age of 100 d. Twelve different craniofacial dimensions, tibia and body length, and final weight were recorded. Female and male groups were analyzed separately. As an expression of catch-up growth, most of the body and craniofacial structures returned to the control level by 100 d of age. A clear sex-dependency was seen in the measurements which remained reduced so that females seemed to catch-up better than males. The timing of the first injection was found to be important for the catch-up growth in the neurocranial area.

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Section: Discussionsupporting

confidence: 90%

Catch‐up growth and craniofacial dimensions following administrationof the antineoplastic agent vincristine to young rats

Karsila

Jahnukainen

Salmi

et al. 2000

European J Oral Sciences

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“…A significant proportion of patients with radiation-induced GH deficiency and disturbances in GH pulsatility (Spoudeas et al 1996) can release GH in response to an acute bolus of GH secretagogues (Ogilvy-Stuart et al 1994); they may be candidates for chronic GHRH analogue treatment to build up their pituitary GH reserve (Ogilvy-Stuart et al 1997, Achermann et al 1999. Schunior et al (1994) used a rodent model of irradiation-induced stunting to evaluate the impact of prior methotrexate or prednisone treatments, and Winterer et al (1988) showed that the radiosensitivity of the GnRH/gonadotroph axis in rodents could be altered by concurrent treatment with GnRH analogues. We hope to use our rodent model to test specific interventions with hypophysiotrophic factors that might prevent or reduce the occurrence, delay the progression, or ameliorate the severity, of long-term multiple endocrine deficits caused by cranial irradiation.…”

mentioning

confidence: 99%

Differential radiosensitivity of hypothalamo-pituitary function in the young adult rat

Robinson

Fairhall²,

Hendry³

et al. 2001

Journal of Endocrinology

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Cranial irradiation in children and adults often results in irreversible hypopituitarism. The earliest and most common endocrine abnormality is GH deficiency, often followed by other pituitary hormone deficits. We investigated whether a similar pattern of progressive hypopituitarism could be reproduced in an animal model. Different doses of cranial irradiation were delivered to the hypothalamo-pituitary region of normal adult male rats, and the effects on their subsequent growth, pituitary weight and hormone contents were studied. Animals received cranial irradiation with 300 kV X-rays at doses of 0, 20, 22 or 24 Gy (n=15 per group) and five animals from each group were killed at 8, 14 or 20 weeks after irradiation. Their anterior pituitary glands were weighed and assayed for GH, LH, TSH, ACTH and prolactin (PRL) content. All three doses of irradiation reduced body weight compared with that in non-irradiated controls and compromised growth between 8 and 20 weeks. Pituitary weight increased between 8 and 20 weeks in control rats, whereas it decreased significantly in the irradiated animals. Irradiation induced time-and dose-dependent changes in pituitary hormone contents. GH and PRL were most sensitive and decreased by more than 90% after irradiation; TSH contents were unaffected 8 weeks after the lowest dose of irradiation, but were reduced at 14 and 20 weeks. LH and ACTH were the slowest to be affected, and only at the greater doses of radiation. Thus progressive multiple pituitary endocrine deficits can be induced differentially in rats by increasing doses of cranial irradiation. This model should prove useful for defining the sites and mechanisms by which cranial irradiation induces neuroendocrine dysfunction.

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“…58 -60 Proton beam radiation can reduce radiation doses to chiasm, pituitary gland, and noninvolved tissues, with high conformity to target volumes, steep dose gradients, and sparing of normal tissue. 61 Potential interventions to decrease radiation injury include gonadotropin-releasing hormone agonists, 62 prednisone, 63 and lithium. 64 Radiation sensitizers permit lower radiation doses but, alternatively, may produce greater late effects.…”

Section: Interventions To Decrease Injurymentioning

confidence: 99%

Mechanisms of Hypothalamic-Pituitary Injury After Oncologic Disease

Rose¹

2008

The Endocrinologist

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Hypopituitarism is a common complication of brain tumors as a consequence of the tumor itself or as a side effect of therapies used in treating the tumor. The mechanism by which such injury occurs is not well understood. Hypothalamic/pituitary damage may follow tumor invasion or anatomic shift in critical brain structures related to pressure from tumor mass, hydrocephalus, surgical traction, ischemia/reperfusion, hemorrhage, vascular damage or stenosis, autoimmune response to injured cells, radiation necrosis, and radiation-induced DNA damage with altered cellular repair mechanisms. Endocrine deficiency is related to the dose of cranial radiation. Other determinants of sensitivity are poorly understood. Growth hormone deficiency is often the first deficiency recognized, but sometimes thyrotropin deficiency occurs first, followed by precocious puberty and adrenocorticotropin deficiency. Gonadotropin deficiency is often recognized in adults first because altered growth velocity is no longer available as a signal. Approaches used to reduce pituitary injury include delay in the use of irradiation until an older age, or choice of other types of irradiation such as conformal radiation, stereotactic radiosurgery, or proton beam therapy. The full manifestation of hypothalamic/pituitary dysfunction can unfold over several decades. At a minimum, annual monitoring of endocrine status is indicated. Learning Objectives• Outline the causes and mechanisms of injury to the hypothalamus and pituitary gland resulting from brain tumors and their treatment.• Describe the development and course of endocrine deficiencies in children who survive brain tumors with the aid of radiotherapy and chemotherapy. • List alternative radiotherapy techniques that hold the potential of limiting radiation injury.

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Radiation Effects on Growth Are Altered in Rats by Prednisolone and Methotrexate

Cited by 29 publications

References 21 publications

Catch‐up growth and craniofacial dimensions following administrationof the antineoplastic agent vincristine to young rats

Catch‐up growth and craniofacial dimensions following administrationof the antineoplastic agent vincristine to young rats

Differential radiosensitivity of hypothalamo-pituitary function in the young adult rat

Mechanisms of Hypothalamic-Pituitary Injury After Oncologic Disease

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