DNA reactivity and in vitro cytotoxicity of the novel antitumor agent 1,5,2,4-dioxadithiepane-2,2,4,4-tetraoxide (NSC-348948) in human embryo cells

Abstract

1,5,2,4-Dioxadithiepane-2,2,4,4-tetraoxide (cyclic-SoSo) is structurally a novel synthetic compound but may functionally act as an alkylating agent. The effects of cyclic-SoSo on DNA were studied in IMR-90 and VA-13 human embryo cells by means of DNA alkaline elution analysis. In contrast to a number of bifunctional alkylating agents, cyclic-SoSo produced no DNA-DNA interstrand cross-links in either cell line, even at concentration which produced a greater than 3 log cell kill. At equimolar concentrations cyclic-SoSo induced DNA-protein cross-links in both cell lines to a similar extent. Frank DNA breaks and alkali-labile DNA lesions were detected in both cell lines. A greater quantity of strand breaks appeared in the IMR-90 than in the VA-13 cell line after exposure to cyclic-SoSo. However, cyclic-SoSo was more cytotoxic to the VA-13 cell line in vitro than to the IMR-90 cell line. Thus cyclic-SoSo may not be a typical bifunctional alkylating agent in that its mechanism of action does not appear to involve DNA interstrand cross-linking.