Kinetic studies of the radical-scavenging activity of estrogens and antiestrogens.

Quinoids, quinoid radicals and phenoxyl radicals formed from estrogens (estrone; diethylstilbestrol, DES) and antiestrogens (tamoxifen; toremifene) may be responsible for adverse effects such as carcinogenesis. The radical-scavenging activity of estrogens and antiestrogens was determined quantitatively by the induction period method for the polymerization of methyl methacrylate initiated by thermal decomposition of 2,2'-azobisisobutyronitrile (AIBN) or benzoyl peroxide (BPO) under nearly anaerobic conditions. The inhibition rate constant (k(inh), x10(-3) M(-1)s(-1)) for estrone, DES, tamoxifen, toremifene and 2,6-di-t-butyl-4-methyphenol (BHT) was 1-3, 2-4, 6-12, 6-13 and 1-2, respectively. The k(inh) for antiestrogens was two-fold greater than that for estrogens or BHT. In contrast, the stoichiometric factor (n, number of free radicals trapped by one mole of antioxidant moiety) for estrone, DES, tamoxifen, toremifene and BHT was 1.2-1.5, 1.8-2.4, 0.5-0.9, 0.4- 0.5 and 1.5-1.9, respectively. The fully oxidized n values for estrone, DES and BHT would be 2, whereas that for antiestrogens would be 1. However, the n values for estrone and antiestrogens were markedly less than 2 and 1, respectively, suggesting a complex oxidation process resulting in the formation of quinoids, quinoid radicals and phenoxyl radicals during the induction period.