| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Laboratory of Molecular Pharmacology, Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute, NIH, Bethesda, Maryland 20014
The formation of DNA cross-links is thought to represent the lethal lesion following exposure of cells to blfunctional alkylating agents. Since differences in rates of formation and repair of cross-links may explain differences in activity of these agents, we have studied these events following exposure of L1210 cells to nitrogen mustard (HN2) and melphalian. With the technique of alkaline elution, it was possible to measure cross-linking at doses that result in relatively little cell kill. Following a 30-min exposure to HN2, DNA cross-links increased for 1 to 2 hr and were then removed by a porcess that was virtually complete in 24 hr. In contrast, following a 30-min exposure to melphalan, cross-link formation increased for 12 hr and removal was much slower than it was for HN2. Comparison of cell survival with cross-linking kinetics suggests that persistence of the cross-links with time is an important factor in determining lethality.
1 To whom requests for reprints should be addressed.
Received 7/ 5/77. Accepted 3/ 1/78.
This article has been cited by other articles:
|
|
 |
|
  S. M. Hillier, J. C. Marquis, B. Zayas, J. S. Wishnok, R. G. Liberman, P. L. Skipper, S. R. Tannenbaum, J. M. Essigmann, and R. G. Croy DNA adducts formed by a novel antitumor agent 11{beta}-dichloro in vitro and in vivo. Mol. Cancer Ther., April 1, 2006; 5(4): 977 - 984. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Wong, C. Lee, and I. F. Tannock Reduction of Intracellular pH as a Strategy to Enhance the pH-Dependent Cytotoxic Effects of Melphalan for Human Breast Cancer Cells Clin. Cancer Res., May 1, 2005; 11(9): 3553 - 3557. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Gould, C. Nixon, and M. J. Tilby p53 Elevation in Relation to Levels and Cytotoxicity of Mono- and Bifunctional Melphalan-DNA Adducts Mol. Pharmacol., November 1, 2004; 66(5): 1301 - 1309. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. L. Souliotis, M. A. Dimopoulos, and P. P. Sfikakis Gene-specific Formation and Repair of DNA Monoadducts and Interstrand Cross-links after Therapeutic Exposure to Nitrogen Mustards Clin. Cancer Res., October 1, 2003; 9(12): 4465 - 4474. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Panasci, J.-P. Paiement, G. Christodoulopoulos, A. Belenkov, A. Malapetsa, and R. Aloyz Chlorambucil Drug Resistance in Chronic Lymphocytic Leukemia: The Emerging Role of DNA Repair Clin. Cancer Res., March 1, 2001; 7(3): 454 - 461. [Abstract] [Full Text]
|
|
|
|
|
|
F. Pinguet, S. Culine, F. Bressolle, C. Astre, M.-P. Serre, C. Chevillard, and M. Fabbro A Phase I and Pharmacokinetic Study of Melphalan Using a 24-hour Continuous Infusion in Patients with Advanced Malignancies Clin. Cancer Res., January 1, 2000; 6(1): 57 - 63. [Abstract] [Full Text]
|
|
|
|
 |
|
 C. Muller, G. Christodoulopoulos, B. Salles, and L. Panasci DNA-Dependent Protein Kinase Activity Correlates With Clinical and In Vitro Sensitivity of Chronic Lymphocytic Leukemia Lymphocytes to Nitrogen Mustards Blood, October 1, 1998; 92(7): 2213 - 2219. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
