Effects of danazol on proliferation and viability of 7,12-dimethylbenz(a)anthracene-induced mammary tumours in rats

The suppressive effects of danazol, an isoxazol derivative of a synthetic steroid 17 alpha-ethinyltestosterone, on cellular viability and DNA synthesis in 7,12-dimethylbenz(a)anthracene induced mammary tumours were investigated in adult female rats by enzyme assays and immunohistochemistry with bromodeoxyuridine (BrdU). Rats treated with danazol for 30 days showed a decrease of plasma levels of luteinizing hormone and estradiol associated with a dysfunction in hypothalamo-hypophysial-gonadal axis, resulting in lower activities in succinate dehydrogenase and thymidine kinase, and a reduction of BrdU-immunoreactive cells in mammary tumours compared with the control, i.e., decreases of viability and pyrimidine nucleotide synthesis in tumour cells in danazol-treated rats.