Low-level binding of halothane metabolites to rat liver histones in vivo.
Edmunds-HN; Trudell-JR; Cohen-EN
Anesthesiology 1981 Apr; 54(4):298-304
Halothane (151677) metabolite binding to liver histones was investigated in-vivo in rats. Adult male Fischer-344-rats were pretreated 24 hours prior to halothane exposure with subcutaneous administration of either a suspension of triiodothyronine, glucagon and heparin (to stimulate liver growth) or with 0.5 milliliters saline as a control. Rats were administered 14 microliters (132 micromoles) of carbon-14 labeled halothane in a delivery capsule inserted intraperitoneally. After 1 hour, rats were maintained in an atmosphere of 8 to 10 percent oxygen in nitrogen for 5 hours. Liver homogenates were prepared, and histones were extracted from chromatin. Of the initial 132 micromoles of halothane administered, 1.1 micromoles remained as nonvolatile metabolites in the liver homogenate and 25 picomoles were associated with purified histones. No significant binding to liver cell RNA or DNA was noted. With this low level of histone modification and the lack of convincing evidence of halothane metabolite binding to hepatic nucleic acids, it was deemed unlikely that significant changes occurred in the genome after exposure to halothane. The authors conclude that relatively little covalent modification of chromosomal components results from exposure to halothane metabolites.
NIOSH-Publication; NIOSH-Grant; Pulmonary-system-disorders; DNA-damage; Chromosome-damage; Metabolic-study; Laboratory-animals; Anesthetics; Halogenated-hydrocarbons
Anesthesia Stanford University 300 Pasteur Drive Stanford, Calif 94305
Stanford University, Stanford, California