Search

This study investigated if quinacrine can induce a tumorigenic response in rats when administered in a manner similar to the intended human use for female non-surgical sterilization. Young sexually mature female rats received two doses of quinacrine (or 1% methylcellulose control) into each uterine horn approximately 21days apart, and were observed for 23months after the second dose administration. Dose levels were 0/0, 0/0, 10/10, 70/70, and 70/250–350mg/kg (first dose/second dose), which represent local doses in the uterus at approximate multiples of 1×, 8× and 40× the human dose (mg quinacrine/g uterine weight) used for female non-surgical sterilization. Rats were observed for viability, clinical signs of toxicity, and changes in body weight and food consumption. At necropsy, selected organs were weighed, macroscopic observations were recorded, and tissues were collected, fixed, processed, and examined for microscopic pathologic findings. Acute quinacrine toxicity was evident during the dosing period but did not affect long-term survival. Non-neoplastic findings were more common in treated animals than controls, providing evidence of the appropriateness of the bioassay. The incidence of uncommon tumors of the reproductive tract was similar to controls at doses of 10/10mg/kg but increased with dose level and was significantly greater than controls at ⩾70/70mg/kg. We conclude that two doses of quinacrine administered approximately 21days apart into the uterus of young sexually mature rats at a local dose approximately 8 times the human dose used for non-surgical female sterilization increased the lifetime risk of tumor development in the reproductive tract. [Copyright &y& Elsevier]

Single cutaneous fibers were recorded in the median nerve of the deeply anesthetized rat and the receptor morphology in the forelimb glabrous skin was analyzed to establish a probable correlation between receptor anatomy and physiology. Receptor complexes in the glabrous skin of the rat forelimb were stained immunologically with antibodies NF-200 and PGP-9.5, confirming the presence of Meissner corpuscles and Merkel complexes within the dermal papilla similar to other mammals including primates. Both the Meissner corpuscles and Merkel cell complexes were sparse and located in the pyramidal-shaped palmer pads and the apex of the digit extremities. They were almost totally absent elsewhere in the glabrous skin. No Ruffini receptors or Pacinian corpuscles were found in our samples. A total of 92 cutaneous fibers were retained long enough for analysis. Thirty-five (38%) were characterized as rapidly adapting fibers (RA) and 57 (62%) were slowly adapting afferents (SA). Despite the very limited number of receptors at the tip of the digit, RA receptors outnumbered SA fibers 3.2/1.0. In contrast, SA fibers on the thenar pad outnumbered RA receptors by a ratio of 3–1. Despite the very limited number of low threshold mechanoreceptors in the glabrous skin of the rat forelimb, the prevalence of SA afferents in the palm and more frequent occurrence of RA afferents in the digit extremity suggest differences in functionality both for locomotion and object manipulation. [ABSTRACT FROM AUTHOR]

Dose-dependent modifying effects of quinacrine on induction of preneoplastic liver cell foci were investigated in male F344 rats. Six week old animals were injected i.p. with -nitroso-diethylamine (DEN) at a dose of 200 mg/kg, and starting 2 weeks later, rats were given quinacrine at dietary levels of 20, 100 and 500 p.p.m. for 6 weeks. Groups without either DEN or quinacrine treatment were used as controls. At week 3 following DEN administration, all animals were subjected to two-thirds partial hepatectomy, and after killing the animals at week 8, development of preneoplastic liver cell foci was investigated using the glutathione S-transferase placental form (GST-P) as a marker. The numbers and unit areas of GST-P-positive foci per cm were significantly increased in the DEN/quinacrine (500 p.p.m.) group as compared to DEN-alone group values. An increase in number was also evident in the 100 p.p.m. but not the 20 p.p.m. treated group, no lesions being induced by quinacrine alone (500 p.p.m.). Electron microscopic study confirmed that quinacrine dosedependently induces lipidosis in hepatocytes, i.e. markedly myeloid lamellar cytoplasmic inclusion bodies were observed. The results thus demonstrated that quinacrine treatment enhances GST-P-positive liver cell foci development in a dose-dependent way, this effect presumably being related to the induction of lipidosis. [ABSTRACT FROM PUBLISHER]