DNA cross-linking and monoadduct repair in nitrosourea-treated human tumour cells

摘要: The 1-(2-chloroethyl)-1-nitrosoureas are potent anti-cancer drugs which produce DNA inter-strand cross-links in a two-step reaction sequence. first step was proposed to be an addition of chloroethyl group guanine-O6 position DNA; the second step, occurs over period several hours absence free drug, could then form interstrand cross-link by slow bound with nucleophilic site on opposite strand. delay between formation monoadducts and allows time for repair mechanism, capable removing monoadducts, prevent cross-linking. We recently this mechanism account difference cross-linking normal transformed human cell strain. Day his coworkers (see refs 7, 8 previous paper) found that some tumour strains (designated Mer- phenotype) deficient ability O6-methylguanine lesions DNA. therefore hypothesized function removes residues from would also remove hence chloroethylnitrosourea-induced now present evidence supports hypothesis indicates confers resistance killing chloroethylnitrosourea.