An animal model to study toxicity of central nervous system therapy for childhood acute lymphoblastic leukemia: Effects on growth and craniofacial proportion

Journal Article · Mon Oct 15 04:00:00 EDT 1990 · Cancer Research; (USA)

OSTI ID:6270255

Schunior, A; Zengel, A E; Mullenix, P J; Tarbell, N J; Howes, A; Tassinari, M S ^[1]

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1. Forsyth Research Institute, Boston, MA (USA)

Many long term survivors of childhood acute lymphoblastic leukemia have short stature, as well as craniofacial and dental abnormalities, as side effects of central nervous system prophylactic therapy. An animal model is presented to assess these adverse effects on growth. Cranial irradiation (1000 cGy) with and without prednisolone (18 mg/kg i.p.) and methotrexate (2 mg/kg i.p.) was administered to 17- and 18-day-old Sprague-Dawley male and female rats. Animals were weighed 3 times/week. Final body weight and body length were measured at 150 days of age. Femur length and craniofacial dimensions were measured directly from the bones, using calipers. For all exposed groups there was a permanent suppression of weight gain with no catch-up growth or normal adolescent growth spurt. Body length was reduced for all treated groups, as were the ratios of body weight to body length and cranial length to body length. Animals subjected to cranial irradiation exhibited microcephaly, whereas those who received a combination of radiation and chemotherapy demonstrated altered craniofacial proportions in addition to microcephaly. Changes in growth patterns and skeletal proportions exhibited sexually dimorphic characteristics. The results indicate that cranial irradiation is a major factor in the growth failure in exposed rats, but chemotherapeutic agents contribute significantly to the outcome of growth and craniofacial dimensions.

• OSTI ID: 6270255
• Journal Information: Cancer Research; (USA), Journal Name: Cancer Research; (USA) Vol. 50:20; ISSN 0008-5472; ISSN CNREA
• Country of Publication: United States
• Language: English

Related Subjects

550602 -- Medicine-- External Radiation in Diagnostics-- (1980-)
560152* -- Radiation Effects on Animals-- Animals
62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL GROWTH
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL MODELS
BIOLOGICAL RADIATION EFFECTS
BODY
BODY AREAS
BRAIN
CENTRAL NERVOUS SYSTEM
COMBINED THERAPY
DISEASES
DOSES
FACE
GROWTH
HEAD
HEMIC DISEASES
IMMUNE SYSTEM DISEASES
INHIBITION
LEUKEMIA
MALFORMATIONS
MAMMALS
MEDICINE
NEOPLASMS
NERVOUS SYSTEM
NUCLEAR MEDICINE
ORGANS
PATHOLOGICAL CHANGES
RADIATION DOSES
RADIATION EFFECTS
RADIOINDUCTION
RADIOLOGY
RADIOTHERAPY
RATS
RODENTS
SIDE EFFECTS
SKELETAL DISEASES
SKELETON
THERAPY
VERTEBRATES