This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Gibson, N. W. Articles by Kohn, K. W. Search for Related Content PubMed PubMed Citation Articles by Gibson, N. W. Articles by Kohn, K. W.

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

Laboratory of Molecular Pharmacology, Division of Cancer Treatment, National Cancer Institute, NIH, Bethesda, Maryland 20205

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.

¹ To whom requests for reprints should be addressed. Present address: Department of Pharmacology, Fox Chase Cancer Center, Central and Shelmire Ave., Philadelphia, PA 19111.

Received 9/ 6/85. Revised 12/12/85. Accepted 1/ 7/86.