Enhancing Effects of β‐Estradiol 3–Benzoate but Not Methoxychlor on the Promotion/Progression Stage of Chemically‐induced Mammary Carcinogenesis in Ovariectomized Rats

Modifying effects of β‐estradiol 3–benzoate (EB) and methoxychlor (MXC), a pesticide which possesses weak estrogenic activity, on 7,12–dimethylbenz(a)anthracene (DMBA)‐induced mammary carcinogenesis were investigated in ovariectomized or intact female Sprague‐Dawley rats. Twenty‐eight weeks after a single DMBA (100 mg/kg body weight) initiation, when the incidence of mammary tumor‐bearing rats had reached 75%, a number of the animals were subjected to ovariectomy in order to obtain 3 groups: i) tumor‐bearing, ovariectomized group; ii) tumor‐bearing, intact group; iii) no‐tumor, ovariectomized group. Subsequently animals of each group were subjected to subcutaneous implantation of 0.5 mg EB or given diet containing 1000 ppm MXC for 13 weeks. Although the incidences, multiplicities and volumes of the palpable tumors gradually decreased after ovariectomy, EB treatment stimulated tumor growth in the tumor‐bearing, ovariectomized group thereafter. A similar effect of EB treatment was also observed in the no‐tumor, ovariectomized group. However, MXC did not show any effect in the tumor‐bearing, or no‐tumor ovariectomized groups, except that the multiplicity of tumors was significantly decreased by MXC treatment in the tumor‐bearing, intact group. The results of our study suggest that MXC has no promotion/progression effect, but rather possesses a weak inhibitory effect, whereas the strongly estrogenic substance EB clearly enhanced DMBA‐induced mammary tumorigenesis.