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

• Published in: Cancer research (Chicago, Ill.) Ill.), 1990-10, Vol.50 (20), p.6455-6560
• Main Authors: SCHUNIOR, A, ZENGEL, A. E, MULLENIX, P. J, TARBELL, N. J, HOWES, A, TASSINARI, M. S
• Format: Article
• Language: English
• Subjects: 550602 - Medicine- External Radiation in Diagnostics- (1980-); 560152 - Radiation Effects on Animals- Animals; ANIMAL GROWTH; ANIMALS; Biological and medical sciences; BIOLOGICAL EFFECTS; BIOLOGICAL MODELS; BIOLOGICAL RADIATION EFFECTS; BODY; BODY AREAS; BRAIN; CENTRAL NERVOUS SYSTEM; Cephalometry; Combined Modality Therapy; COMBINED THERAPY; DISEASES; DOSES; Drug toxicity and drugs side effects treatment; FACE; Female; GROWTH; Growth - drug effects; Growth - radiation effects; HEAD; HEMIC DISEASES; Humans; IMMUNE SYSTEM DISEASES; INHIBITION; LEUKEMIA; Male; MALFORMATIONS; MAMMALS; Medical sciences; MEDICINE; Methotrexate - toxicity; NEOPLASMS; NERVOUS SYSTEM; NUCLEAR MEDICINE; ORGANS; PATHOLOGICAL CHANGES; Pharmacology. Drug treatments; Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy; Prednisolone - toxicity; RADIATION DOSES; RADIATION EFFECTS; RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT; RADIOINDUCTION; RADIOLOGY; RADIOLOGY AND NUCLEAR MEDICINE; RADIOTHERAPY; Radiotherapy - adverse effects; RATS; Rats, Inbred Strains; RODENTS; SIDE EFFECTS; SKELETAL DISEASES; SKELETON; Skull - drug effects; Skull - radiation effects; THERAPY; Toxicity: nervous system and muscle; VERTEBRATES
• ISSN: 0008-5472; 1538-7445

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.