Antitumour Activity,Toxicity and Disposition of LS 1727, a Nitroso-Chloroethyl Carbamate of 19-Nortestosterone,in Rats and Mice

Abstract: LS 1727, a nitroso-chloroethyl carbamate of 19-nortestosterone, given intraperitoneally had a high cytostatic activity against some experimental tumours. In vitro studies showed that the tested tumours differed in their ability to hydrolyze LS 1727. The hydrolytic capacity was related to the sensitivity to treatment with LS 1727. Distribution studies with double-labelled LS 1727 demonstrated that the chloroethyl-part of the molecule was retained in dimethylbenz(a)anthracene-induced mammary tumours in the rat. Our findings suggest that the antitumour activity of LS 1727 is exerted by alkylating metabolites released at hydrolysis of the compound. LS 1727 had no oral antitumour activity probably due to pre-systemic hydrolysis. When given intravenously, hydrolysis of LS 1727 in lungs caused severe pulmonary toxicity already at low doses.