title: Effects of Repeated Anesthesia Containing Urethane on Tumor Formation and Health Scores in Male C57BL/6J Mice.
abstract: Repeated injection of urethane (ethyl carbamate) is carcinogenic in susceptible strains of mice. Most recent cancer studies involving urethane-induced tumor formation use p53(+/-) mice, which lack one copy of the p53 tumor suppressor gene. In contrast, the same protocol elicits at most a single tumor in wildtype C57BL/6 mice. The effect of repeatedly injecting urethane as a component of a ketamine-xylazine anesthetic mixture in the highly prevalent mouse strain C57BL/6 is unknown. Male C57BL/6J mice (n = 30; age, 3 mo) were anesthetized once monthly for 4 mo by using 560 mg/kg urethane, 28 mg/kg ketamine, and 5.6 mg/kg xylazine. The physical health of the mice was evaluated according to 2 published scoring systems. The average body condition score (scale, 1 to 5; normal, 3) was 3.3, 3.3, and 3.4 after the 2nd, 3rd, and 4th injections, respectively. The visual assessment score was 0 (that is, normal) at all time points examined. Within 1 wk after the 4th injection, the mice were euthanized, necropsied, and evaluated histopathologically. No histopathologic findings were noteworthy. We conclude that repeated monthly injection with urethane as a component of an anesthetic cocktail does not cause clinically detectable abnormalities or induce neoplasia in C57BL/6J mice. These findings are important because urethane combined with low-dose ketamine, unlike other anesthetic regimens, allows for accurate recording of neuronal activity in both the brain and retina. Longitudinal neuronal recordings minimize the number of mice needed and improve the analysis of disease progression and potential therapeutic interventions.
authors.affiliation: Vanderbilt Eye Institute, Vanderbilt University School of Medicine, Nashville, Tennessee, USA; Vanderbilt Brain Institute, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. Tonia.rex@vanderbilt.edu.
authors.forename: Tonia S
authors.initials: TS
authors.lastname: Rex
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Comparative Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Kelli
authors.initials: K
authors.lastname: Boyd
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Comparative Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Troy
authors.initials: T
authors.lastname: Apple
authors.affiliation: Vanderbilt Eye Institute, Vanderbilt Brain Institute, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Courtney
authors.initials: C
authors.lastname: Bricker-Anthony
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Comparative Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Krystal
authors.initials: K
authors.lastname: Vail
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Comparative Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Wallace
mesh_terms: D000777:Anesthetics / Q000008:administration & dosage* / Q000009:adverse effects*; D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage*; D007649:Ketamine / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL / Q000145:classification; D009369:Neoplasms / Q000139:chemically induced; D014520:Urethane / Q000008:administration & dosage* / Q000009:adverse effects*; D014991:Xylazine / Q000008:administration & dosage
chemical_list: D000777:Anesthetics; D002273:Carcinogens; D014991:Xylazine; D014520:Urethane; D007649:Ketamine