Alteration of cellular oncogene expression in L1210 cells by a nitrosourea analog of thymidine.

3'[3-(2-Chloroethyl)-3'nitrosoureido]-3'-deoxythymidine (3'-CTNU), a chloroethylnitrosourea analog of thymidine, is a potent antineoplastic agent against murine leukemia L1210. In this study, we have examined the effects of 3'-CTNU on cellular oncogene (proto-oncogene) expression. We found that the expression of the c-myb proto-oncogene was dramatically enhanced in a concentration- and time-dependent manner by 3'-CTNU in murine leukemia L1210 cells, whereas the expression of the c-myc proto-oncogene was suppressed. The enhancement of c-myb gene expression was found to be cell type-specific and to involve an increase of the c-myb transcription rate rather than an alteration of c-myb gene structure or increased stability of c-myb mRNA. Further analysis demonstrated that the altered c-myb gene expression was largely due to the presence of 3'-amino-3'-deoxythymidine, a decomposition product of 3'-CNTU. The expression of five other proto-oncogenes was unaffected by 3'-CTNU treatment. Our study showed that an antineoplastic agent can increase or decrease the expression of proto-oncogenes.