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Gene Expression Caused by Alkylating Agents and cis-Diamminedichloroplatinum(II) in Escherichia coli¹

Departments of Medicine and Pharmacology [R. J. F.] and Molecular Genetics and Microbiology [J. C., M. R. V.], University of Massachusetts Medical School, Worcester, Massachusetts 01655

Previous work has demonstrated heterogeneous effects of methylating agents on induction of DNA damage inducible genes in Escherichia coli. These studies employed E. coli mutants that have fusions of the lac operon to genes induced by treatment with sublethal levels of alkylating agents. These mutants were selected from random insertions of the Mudl (Ap^r lac) phage by screening for induction of ß-galactosidase activity in the presence of methylmethanesulfonate or N-methyl-N'-nitro-N-nitrosoguanidine. The current report extends these findings by analyzing gene expression caused by mechlorethamine, chloroethylnitrosoureas and cis-diamminedichloroplatinum(II) (cis-DDP). The results demonstrate heterogeneous effects by these agents on gene expression. While 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea induces alkA, other nitrosoureas, mechlorethamine, and cis-DDP do not cause expression of this gene. Further, while all nitrosoureas caused expression of aidC, mechlorethamine and cis-DDP did not. Lastly, cis-DDP caused marked expression of a sulA fusion mutant while not inducing any of the other E. coli fusion mutants.

¹ Supported by NIH Grant GM-37052 (M. R. V.) and USPHS Grant R32CA38613 (R. J. F.).

² To whom requests for reprints should be addressed, at Division of Oncology, 55 Lake Avenue North, Worcester, MA 01655.

Received 12/10/87. Revised 5/18/88. Accepted 5/27/88.