Inhibitory Effects of Nabumetone, a Cyclooxygenase‐2 Inhibitor, and Esculetin, a Lipoxygenase Inhibitor, on N‐Methyl‐N‐nitrosourea‐induced Mammary Carcinogenesis in Rats

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Abstract
We investigated the modifying effects of nabumetone, a relatively selective cyclooxygenase‐2 inhibitor, and esculetin, a lipoxygenase inhibitor, on N‐methyl‐N‐nitrosourea(MNU)‐induced mammary carcinogenesis in female Sprague‐Dawley rats. A total of 124 rats, 6 weeks old, were divided into 6 groups. At 50 days of age, groups 1, 2, and 3 were treated with MNU (50 mg/kg body weight) by subcutaneous injection. From the age of 8 weeks, groups 2 and 4 were given 0.03% nabumetone in the diet and groups 3 and 5 were given 0.03% esculetin in the diet. All rats were necropsied at the termination (25 weeks after the start of experiment). The incidence and multiplicity of neoplasms in group 2 were significantly smaller than those in group 1 (P<0.005 and P<0.001, respectively). The incidence of neoplasms in group 3 was also significantly smaller than that in group 1 (P<0.05). These results indicate that the intake of nabumetone or esculetin during the time corresponding to the post initiation phase has a chemopreventive effect on MNU‐induced mammary carcinogenesis in rats.