<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Souliotis, V.L.</style></author><author><style face="normal" font="default" size="100%">Dimopoulos, M.A.</style></author><author><style face="normal" font="default" size="100%">Sfikakis, P.P.</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Gene-specific formation and repair of DNA monoadducts and interstrand cross-links after therapeutic exposure to nitrogen mustards</style></title><secondary-title><style face="normal" font="default" size="100%">Clinical Cancer Research</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2003</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2003</style></date></pub-dates></dates><urls><web-urls><url><style face="normal" font="default" size="100%">https://www.scopus.com/inward/record.uri?eid=2-s2.0-0141995075&amp;partnerID=40&amp;md5=8072e6c71ccd553cb77a46a8b4a683fb</style></url></web-urls></urls><volume><style face="normal" font="default" size="100%">9</style></volume><pages><style face="normal" font="default" size="100%">4465 - 4474</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">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 ± 0.3 h (p53) or 18.8 ± 1.5 h (N-ras) for monoadducts and 12.4 ± 0.8 h (p53) or 14.1 ± 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.</style></abstract><issue><style face="normal" font="default" size="100%">12</style></issue><notes><style face="normal" font="default" size="100%">Cited By :26Export Date: 21 February 2017</style></notes></record></records></xml>