Interstitial quinacrine for elimination of abnormal tissue; therapy of experimental glioma.
BACKGROUND
When quinacrine is injected interstitially, an intense migration of leukocytes and accumulation of various lymphokines is obtained locally, and the reaction is followed by cicatricial fibrosis. This property has been used in humans to induce tubal fibrosis in women and pleurodesis in patients with pleural effusion.


METHODS
In a controlled study, a single dose of 150 mg of quinacrine was injected interstitially into a C6 glioma implanted in the subcutaneous tissue of Wistar rats. Changes in size, histologic variations, and microscopic characteristics of leukocyte subpopulations infiltrating the tumor were studied by immunohistochemistry. Tumor necrosis factor and interleukin-1 beta were measured at different times in tumor homogenates.


RESULTS
The day after the injection of quinacrine, infiltration of leukocytes and macrophages was observed, accompanied by an accumulation of proinflammatory endogenous cytokines. Tumoral necrosis soon ensued; complete tumor disappearance was obtained in 72% of the animals. Cicatrization proceeded without injury of perilesional structures. In all controls injected with the vehicle, a large tumor developed (P <.0001).


CONCLUSIONS
Quinacrine, when administered interstitially in a single dose, elicits an intense local recruitment and proliferation of activated immune cells that, at the dose used in this study, induces tissue necrosis within a radius of 1 cm around the site of quinacrine injection, leaving the surrounding tissue unharmed.
Sotelo
J
J
Neuroimmunology Unit, National Institute Of Neurology and Neurosurgery, Universidad Nacional Autonoma De Mexico.
Guevara
P
P
Reyes
S
S
Arrieta
O
O
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002921:Cicatrix; D016207:Cytokines / Q000032:analysis; D005110:Extracellular Space; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007267:Injections; D007962:Leukocytes / Q000473:pathology; D011796:Quinacrine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D016207:Cytokines; D011796:Quinacrine