Anticarcinogenic activity of quinacrine in the rat mammary gland.

Mammary carcinogenesis studies were conducted to determine the chemopreventive activity of quinacrine, an antimalarial drug which suppresses the production of arachidonic acid from phospholipid through inhibition of phospholipase A2. Beginning 1 week after a single i.v. dose of N-methyl-N-nitrosourea (MNU), female Sprague-Dawley rats were fed a semi-purified diet supplemented with 0 or 75 mg quinacrine/kg diet. Quinacrine reduced cancer incidence and carcinoma multiplicity in rats administered 20 mg MNU/kg body wt, but had no inhibitory activity in rats treated with 50 mg MNU/kg. These data suggest that pathways of arachidonic acid metabolism in addition to cyclooxygenase present useful targets for mammary cancer chemoprevention. However, the chemopreventive activity of quinacrine may be limited by toxicity.