Nordihydroguaiaretic acid suppression of rat mammary carcinogenesis induced by N-methyl-N-nitrosourea.

The activity of the lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA), as a cancer chemopreventive agent in the rat mammary gland was determined. Beginning 1 week after a single i.v. dose of 20 or 50 mg N-methyl-N-nitrosourea (MNU)/kg body wt., female Sprague-Dawley rats were fed a semi-purified diet supplemented with 0 or 1000 mg NDGA/kg diet. At both MNU dose levels, groups receiving NDGA developed significantly fewer mammary cancers than did dietary controls; NDGA induced no gross or organ-specific toxicity. These data implicate lipoxygenase products in the process of mammary cancer induction, and suggest an additional enzymatic target for the design of chemopreventive drugs.