IN-VITRO TRANSCRIPTION TERMINATION BY N,N'-BIS(2-CHLOROETHYL)-N-NITROSOUREA-INDUCED DNA LESIONS

N,N'-Bis(2-chloroethyl)-N-nitrosourea (BCNU) and its derivatives are c hemotherapeutic DNA-damaging agents that generate a variety of monoadd ucts, intrastrand cross-links, and interstrand cross-links. The cytoto xic potential of the compounds has been linked to their ability to for m DNA interstrand cross-links, which presumably inhibit subsequent DNA replication. To address the possibility that BCNU-induced lesions may also influence other DNA-directed actions such as transcription, and to identify the DNA lesions involved, a synthetic DNA template contain ing phage RNA polymerase promoters at both ends was incubated with BCN U and, after drug removal, transcribed in vitro. For comparison, simil ar studies were carried out with cis-diamminedichloroplatinum(ll) and trans-diamminedichloroplatinum(II), which are known to induce defined transcription-terminating lesions. The results suggest that BCNU, like platinum compounds, can induce lesions resulting in termination of tr anscription in vitro, although the predominant transcription-terminati ng lesions, unlike those produced by cis-diamminedichloroplatinum(ll), most likely represent interstrand DNA cross-links.