Inhibitory effects of nabumetone, a cyclooxygenase-2 inhibitor, and esculetin, a lipoxygenase inhibitor, on N-methyl-N-nitrosourea-induced mammary carcinogenesis in rats.
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.
Matsunaga
K
K
First Department of Pathology, Gifu University School of Medicine.
Yoshimi
N
N
Yamada
Y
Y
Shimizu
M
M
Kawabata
K
K
Ozawa
Y
Y
Hara
A
A
Mori
H
H
D000818:Animals; D002074:Butanones / Q000627:therapeutic use*; D002273:Carcinogens; D002455:Cell Division; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D004791:Enzyme Inhibitors; D005260:Female; D007527:Isoenzymes; D016859:Lipoxygenase Inhibitors / Q000627:therapeutic use; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D008770:Methylnitrosourea; D000077430:Nabumetone; D011451:Prostaglandin-Endoperoxide Synthases; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014468:Umbelliferones / Q000627:therapeutic use*
D002074:Butanones; D002273:Carcinogens; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D016859:Lipoxygenase Inhibitors; D014468:Umbelliferones; D008770:Methylnitrosourea; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000077430:Nabumetone; C007628:esculetin