Combined treatment with radioestradiol-lucanthone in mouse C3HBA mammary adenocarcinoma and with estradiol-lucanthone in an estrogen bioassay

Abstract

C3H female mice bearing transplantable estrogen-nondependent adenocarcinomas were treated subcutaneously with either estradiol, tritiated ( 3H)estradiol, lucanthone, 3H-estradiol followed by lucanthone, or lucanthone followed by 3H-estradiol. Tumor growth and host survival were ascertained. As single agents, lucanthone or 3H-estradiol had slight tutor-inhibiting effects with small tumors. Combined treatment with radioestrogen followed by htcatlthone 4 hrs later blocked early tumor growth for several days and permanently reduced the growth rate thereafter; it also lengthened survival by some 67%. On the other hand, combined treatment with lucanthone followed 1 hr later by 3H-estradiol did not have the same effect. The increase in adrenal gland weight that occurs as this tumor grows was significantly reduced by treatment with lucanthone, and more so by 3HE2…..+Lu; both of these treatmelnts also depressed the lymphatic system. It is suggested that the antitumor effects observed may be mediated-systemically via the adrenal. None of the treatments were effective against advanced tumors. Lucantbone was also administered subcutaneously to w female Swiss mice in conjunction with estradiol. Evidence showed that lucanthone interferes with the immature mouse uterine weight response to estrogen, especially what given 1 hr before the hormone. Although an estrogen dose-response relationship was demonstrated for all groups, the hormone and the DNA intercalating agent interfered with each other in a way that suggests possiblle steric or competitive inhibition. Thus lucanthone modulates two estrogen effects, namely, the effect of estrogen out an estrogen-response tissue (uterine weight, especially when given prior to the hormone), and the effect of radioestrogen on an estrogen-nondependent antonomous tumor (when given after the hormone). A novel antitumor strategy, here called radiocytochemotherapy, is described, and possible applications to human tumors are discussed.