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When human L1210 cells were selected for resistance to 1,2-bis(2-chloroethyl)-3-nitrosourea (BCNU) during 6 months of continuous cultivation, a threefold to eightfold increase in BCNU resistance was detected. Similar results were obtained when several other pairs of parental and BCNU-resistant L1210 cell lines were compared. It has been reported that cell lines resistant to nitrosourea derivatives carry a mutant enzyme to detoxify the carcinogen, the bacterial nitroreductase. Thus, a loss of this enzymatic activity in BCNU-resistant cells might also contribute to their increased resistance to BCNU. However, the activities of four important enzymes in the salvage pathway and glutathione-S-transferase (GST) were comparable in sensitive and resistant L1210 cells, suggesting that, except for the above-mentioned enzyme, no major alterations are involved in the increased resistance. The mRNA levels of the genes coding for glutathione reductase and for alkyl-DNA-protein-synthase were found to be comparable in sensitive and resistant cells. Therefore, mRNA levels and gene expression of proteins synthesized in the same cell seem to be dissociated in some way. A comparison between the rates of DNA damage (as determined by the analysis of alkaline- and neutral eluates) and of BCNU resistance in sensitive and resistant cells revealed a dissociation between the repair of DNA damage and the development of BCNU resistance. Accordingly, the present results suggest that the high resistance of L1210 cells to BCNU can occur either by changing gene transcription or mRNA stability or protein translation.Frequent isolations of Mycobacterium avium-intracellulare complex from patients with inflammatory bowel disease.