@article {8051,
	title = {Gene-specific formation and repair of DNA monoadducts and interstrand cross-links after therapeutic exposure to nitrogen mustards},
	journal = {Clinical Cancer Research},
	volume = {9},
	year = {2003},
	note = {Cited By :26Export Date: 21 February 2017},
	month = {2003},
	pages = {4465 - 4474},
	abstract = {Purpose: To investigate the possibility of measuring the gene-specific DNA damage after therapeutic exposure to nitrogen mustards and to examine its relationship with the clinical response. Experimental Design: The kinetics of gene-specific monoadducts and interstrand cross-link formation/repair were measured in the p53 and N-ras genes. DNA extracted from human peripheral lymphocytes following in vitro exposure to melphalan or therapeutic exposure to melphalan or cyclophosphamide was used. Results: When lymphocytes were treated in vitro with biologically relevant doses of melphalan, monoadducts accumulated rapidly in both p53 and N-ras genes, reaching maximal levels within 2 h, whereas the highest interstrand cross-link levels were found within 8 h. Thereafter, the adducts were repaired with half-lives of 14.5 {\textpm} 0.3 h (p53) or 18.8 {\textpm} 1.5 h (N-ras) for monoadducts and 12.4 {\textpm} 0.8 h (p53) or 14.1 {\textpm} 2.2 h (N-ras) for interstrand cross-links. Moreover, peak levels of monoadducts in both genes were observed 2 h after treatment in peripheral leukocytes from patients with multiple myeloma treated with high-dose i.v. melphalan, supported by autologous stem cell transplantation, whereas interstrand cross-links were maximal within 8 h. Of seven patients examined, the three who showed the least levels of DNA damage did not respond to the high-dose melphalan. Conclusions: This is the first report showing that it is feasible to measure gene-specific DNA damage in a readily accessible tissue of humans exposed to bifunctional alkylating drugs and to examine, at the level of the individual patient, the relationships between the induction/repair of cytotoxic DNA damage and clinical response or long-term complications.},
	url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-0141995075\&partnerID=40\&md5=8072e6c71ccd553cb77a46a8b4a683fb},
	author = {Souliotis, V.L. and Dimopoulos, M.A. and Sfikakis, P.P.}
}
