title: An alternative interpretation of, "A lifetime cancer bioassay of quinacrine administered into the uterine horns of female rats".
abstract: This companion article offers an alternative interpretation for the quinacrine-induced uterine tumors observed in a 2-year bioassay in rats (CaBio, Cancel et al., 2010), and provides additional data from two new experiments that support a different interpretation and analysis. Our major premise is that the design of the Cancel et al. bioassay was flawed, particularly regarding dose selection that allowed for misinterpretation of carcinogenic activity. We feel the totality of the information provided herein dictates that the doses (70/70, 70/250 and 70/350 mg/kg quinacrine) causing uterine tumors in their study clearly exceeded the maximum tolerated dose (MTD) typically administered in chronic cancer studies. Our new data support this conclusion and serve to explain the development of lesions, especially the uterine tumors, they have reported. We argue that the rat uterus is not a valid surrogate for the human fallopian tube. Further, we maintain that quinacrine is not genotoxic in vivo, as suggested in their paper. In summary, we believe that quinacrine is not carcinogenic in rats at doses that do not exceed the MTD.
authors.affiliation: ToxPath Inc., 3028 Ethan Lane, Raleigh, NC 27613, USA. toxpathmcc@bellsouth.net
authors.forename: Ernest E
authors.initials: EE
authors.lastname: McConnell
authors.forename: Jack
authors.initials: J
authors.lastname: Lippes
authors.forename: Roger G
authors.initials: RG
authors.lastname: Growe
authors.forename: Patricia
authors.initials: P
authors.lastname: Fail
authors.forename: Michael I
authors.initials: MI
authors.lastname: Luster
authors.forename: Errol
authors.initials: E
authors.lastname: Zeiger
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D008136:Longevity; D011796:Quinacrine / Q000008:administration & dosage* / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014594:Uterine Neoplasms / Q000139:chemically induced* / Q000473:pathology; D014599:Uterus / Q000187:drug effects* / Q000473:pathology
chemical_list: D011796:Quinacrine