Effect of Biological Time on the Determination of the LD50 of 5-Fluorouracil in MiceBurns E.R. · Beland S.S.
Department of Anatomy, University of Arkansas for Medical Sciences, Little Rock, Ark., USA
The LD50 was determined for 5-fiuorouracil (FU) in mice at 11.00 and 23.00 h during one 24-hour period. These times were chosen because in mice kept on a light-dark cycle, with lights on from 06.00 to 18.00 h, the natural circadian rhythm in DNA synthetic activity in many different normal organs attains peak levels around 24.00 h (mid-dark) and through levels around 12.00 h (mid-light). The LD50 of FU, in milligrams per kilogram body weight, was much higher (450–500 mg/kg) at 11.00 than at 23.00 h (250–300 mg/kg). Since the biology of the living animal oscillates significantly on a daily or circadian basis, it is understandable that the degree of susceptibility or resistance to drugs should also fluctuate over the circadian period. Determination of the LD50 of a drug at that point in time when the animal is naturally resistant to that drug will result is a false appraisal of the toxic effects to the drug. To assess correctly the risk a drug poses, it should be tested at its time of maximal susceptibility in the living animal.
© 1984 S. Karger AG, Basel
E.R. Burns, Department of Anatomy, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (USA)
Received: July 13, 1983
Accepted: August 23, 1983
Published online: June 04, 2008
Number of Print Pages : 5
Pharmacology (International Journal of Experimental and Clinical Pharmacology)
Vol. 28, No. 5, Year 1984 (Cover Date: 1984)
Journal Editor: Donnerer J. (Graz), Billingsley M.L. (Hershey, Pa.), Maeyama K. (Matsuyama)
ISSN: 0031–7012 (Print), eISSN: 1423–0313 (Online)
For additional information: http://www.karger.com/PHA