This Article Full Text 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 HighWire Citing Articles via Google Scholar Google Scholar Articles by Mertins, S. D. Articles by Bates, S. E. Search for Related Content PubMed PubMed Citation Articles by Mertins, S. D. Articles by Bates, S. E.

¹ Cancer Therapeutics Branch, ² Developmental Therapeutics Program, and ³ Laboratory of Molecular Pharmacology, National Cancer Institute, NIH, Bethesda, Maryland

Requests for reprints: Susan D. Mertins, Screening Technologies Branch, National Cancer Institute-Frederick, Building 440, P.O. Box B, Frederick, MD 21702. Phone: 301-846-7245; Fax: 301-846-6775. E-mail: smertins{at}mail.ncifcrf.gov

We identified five structurally related dimethane sulfonates with putative selective cytotoxicity in renal cancer cell lines. These compounds have a hydrophobic moiety linked to a predicted alkylating group. A COMPARE analysis with the National Cancer Institute Anticancer Drug Screen standard agent database found significant correlations between the IC₅₀ of the test compounds and the IC₅₀ of alkylating agents (e.g., r = 0.68, P < 0.00001 for chlorambucil). In this report, we examined whether these compounds had activities similar to those of conventional alkylating agents. In cytotoxicity studies, chlorambucil-resistant Walker rat carcinoma cells were 4- to 11-fold cross-resistant to the test compounds compared with 14-fold resistant to chlorambucil. To determine effects on cell cycle progression, renal cell carcinoma (RCC) line 109 was labeled with bromodeoxyuridine prior to drug treatment. Complete cell cycle arrest occurred in cells treated with an IC₉₀ dose of NSC 268965. p53 protein levels increased as much as 5.7-fold in RCC line 109 and as much as 20.4-fold in breast cancer line MCF-7 following an 18-hour drug exposure. Finally, DNA-protein cross-links were found following a 6-hour pretreatment with all compounds. Thus, the dimethane sulfonate analogues have properties expected of some alkylating agents but, unlike conventional alkylating agents, appear to possess activity against RCC.

Note: T.G. Myers is currently at the Microarray Research Facility, National Institute for Allergy and Infectious Diseases, NIH, Bethesda, MD.

Received 4/28/03; revised 2/11/04; accepted 5/ 3/04.

This article has been cited by other articles:

				V. Probin, Y. Wang, A. Bai, and D. Zhou Busulfan Selectively Induces Cellular Senescence but Not Apoptosis in WI38 Fibroblasts via a p53-Independent but Extracellular Signal-Regulated Kinase-p38 Mitogen-Activated Protein Kinase-Dependent Mechanism J. Pharmacol. Exp. Ther., November 1, 2006; 319(2): 551 - 560. [Abstract] [Full Text] [PDF]