Role of uptake of (14C)valine into protein in the development of tolerance to diisopropylphosphorofluoridate (DFP) toxicity

Journal Article · Tue Jul 01 04:00:00 EDT 1986 · Toxicol. Appl. Pharmacol.; (United States)

DOI:https://doi.org/10.1016/0041-008X(86)90260-7· OSTI ID:5143762

Gupta, R C; Dettbarn, W D

In a subchronic toxicity study male Sprague-Dawley rats were daily treated with diisopropylphosphorofluoridate (DFP) (0.5 mg/kg, sc) for 14 days. Maximum signs of anticholinesterase toxicity were observed during Days 4 and 5 comparable to those seen 10-15 min following a single sublethal dosage (1.5 mg DFP/kg, sc). Signs disappeared after Days 6-7 of exposure and rats became apparently normal during the remainder of the treatment period. Significant hypothermia was seen following the second to fifth doses with maximum effect after the fifth injection. Subsequent injections of DFP did not cause any reduction in temperature. Incorporation of (/sup 14/C)valine was measured 24 hr after the 5th and 14th injections of DFP, at a time when body temperature had recovered to control values. The rate of in vivo incorporation of (/sup 14/C)valine was measured 0.5, 1.0, and 2.0 hr after a subcutaneous injection of L-(1-/sup 14/C)valine at a dose of 5 microCi/mmol/100 g body wt. After five injections the rate of L-(1-/sup 14/C)valine uptake into the free amino acid pool and the incorporation into the protein bound pool was significantly (p less than 0.01) reduced in discrete brain regions, liver, kidney, and skeletal muscles. At the end of the 14-day treatment, protein synthesis in all the skeletal muscles tested had recovered completely (p greater than 0.01) to the values of nontreated control animals. In brain, liver, and kidney, however, no recovery was seen during this period. The recovery of protein synthesis in skeletal muscle may be one of the mechanisms that lead to tolerance development during prolonged administration of subacute concentrations of DFP.

• OSTI ID: 5143762
• Journal Information: Toxicol. Appl. Pharmacol.; (United States), Journal Name: Toxicol. Appl. Pharmacol.; (United States) Vol. 3; ISSN TXAPA
• Country of Publication: United States
• Language: English

Related Subjects

550501 -- Metabolism-- Tracer Techniques
560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINO ACIDS
ANIMALS
BIOLOGICAL RECOVERY
BODY
BODY TEMPERATURE
BRAIN
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
DIGESTIVE SYSTEM
GLANDS
HYPOTHERMIA
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIVER
MAMMALS
NERVOUS SYSTEM
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC FLUORINE COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANS
PROTEINS
RATS
RECOVERY
RODENTS
TOLERANCE
TOXICITY
TRACER TECHNIQUES
UPTAKE
VALINE
VERTEBRATES