An animal model to study toxicity of central nervous system therapy for childhood acute lymphoblastic leukemia: Effects on behavior

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

OSTI ID:6320420

Mullenix, P J; Kernan, W J; Tassinari, M S; Schunior, A; Waber, D P; Howes, A; Tarbell, N J ^[1]

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

Central nervous system prophylactic therapy used in the treatment of acute lymphoblastic leukemia can reduce intelligence quotient scores and impair memory and attention in children. Cranial irradiation, intrathecal methotrexate, and steroids are commonly utilized in acute lymphoblastic leukemia therapy. How they induce neurotoxicity is unknown. This study employs an animal model to explore the induction of neurotoxicity. Male and female Sprague-Dawley rats at 17 and 18 days of age were administered 18 mg/kg prednisolone, 2 mg/kg methotrexate, and 1000 cGy cranial irradiation. Another 18-day-old group was administered 1000 cGy cranial irradiation but no drugs. Matching controls received saline and/or a sham exposure to radiation. All animals at 6 weeks and 4 months of age were tested for alterations in spontaneous behavior. A computer pattern recognition system automatically recorded and classified individual behavioral acts displayed during exploration of a novel environment. Measures of behavioral initiations, total time, and time structure were used to compare treated and control animals. A permanent sex-specific change in the time structure of behavior was induced by the prednisolone, methotrexate, and radiation treatment but not by radiation alone. Unlike hyperactivity, the effect consisted of abnormal clustering and dispersion of acts in a pattern indicative of disrupted development of sexually dimorphic behavior. This study demonstrates the feasibility of an animal model delineating the agent/agents responsible for the neurotoxicity of central nervous system prophylactic therapy.

• OSTI ID: 6320420
• 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

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62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
BEHAVIOR
BIOLOGICAL EFFECTS
BIOLOGICAL MODELS
BIOLOGICAL RADIATION EFFECTS
BODY
BRAIN
CENTRAL NERVOUS SYSTEM
COMBINED THERAPY
COMPUTERIZED SIMULATION
DISEASES
HEMIC DISEASES
IMMUNE SYSTEM DISEASES
LEUKEMIA
MENTAL DISORDERS
NEOPLASMS
NERVOUS SYSTEM
NERVOUS SYSTEM DISEASES
ORGANS
RADIATION EFFECTS
SIDE EFFECTS
SIMULATION
THERAPY