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A One-Year Neonatal Mouse Carcinogenesis Study of Quinacrine DihydrochlorideFamily Health International, Research Triangle Park, North Carolina, USA
Covance Laboratories, Harrogate, North Yorkshire, England
J. Dillberger, LLC, Nashville, Indiana, USA
Family Health International, Research Triangle Park, North Carolina USA
McClain Associates, Randolph, New Jersey, USA Correspondence: Address correspondence to Aida M. Cancel, PhD, P.O. Box 13950, Research Triangle Park, NC 27709, USA. E-mail:acancel{at}fhi.org
Quinacrine is an acridine derivative under investigation for its use in nonsurgical female sterilization. Safety issues regarding the carcinogenic potential of quinacrine have been raised because it is mutagenic and clastogenic in vitro. The objective of the study was to evaluate the carcinogenic potential of quinacrine dihydrochloride (quinacrine) in neonatal mice treated with single intraperitoneal doses on postpartum days 8 and 15 and observed for 52 weeks. Neonatal Crl: CD-1 mice of each sex were randomly allocated into four treatment groups (0, 10, 50, and 150 mg/kg), dosed twice with quinacrine suspended in carboxymethylcellulose, observed for 52 weeks post dose, and then euthanized, necropsied, and subjected to a full histopathological examination. In male mice, tumor incidence was not significantly increased at any site at any dose level. In female mice, the incidence of benign uterine endometrial stromal polyps was slightly greater at the mid and high dose (
Key Words: Carcinogenesis • Endometrial Stromal Polyps • Neonatal Mouse • Quinacrine • Uterus
International Journal of Toxicology, Vol. 25, No. 2,
109-118 (2006) |
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50 mg/kg), as was the incidence of endometrial hyperplasia. The incidence of polyps in these groups was not significantly greater than in controls by pair-wise comparison but was significantly greater (p = .042) by the linear trend test. The authors conclude that quinacrine administered twice to neonatal mice may have enhanced or accelerated the development of endometrial hyperplasia and uterine stromal polyps at higher doses. Because uterine stromal polyps are a commonly observed benign tumor in older mice, the significance of this finding is unclear and will require a weight of evidence evaluation for a conclusion on the carcinogenic potential of quinacrine.